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Mary E Klotman

R.J. Reynolds Distinguished Professor of Medicine
Medicine, Infectious Diseases
DUMC 2927, Davison Building Room 125, Durham, NC 27710
Davison Building Room 125, Box 2927, Durham, NC 27710

Selected Publications


Integrase Defective Lentiviral Vector Promoter Impacts Transgene Expression in Target Cells and Magnitude of Vector-Induced Immune Responses.

Journal Article Viruses · November 14, 2023 Integrase defective lentiviral vectors (IDLVs) are a promising vaccine delivery platform given their ability to induce high magnitude and durable antigen-specific immune responses. IDLVs based on the simian immunodeficiency virus (SIV) are significantly mo ... Full text Link to item Cite

HIV-1 infection of renal epithelial cells: 30 years of evidence from transgenic animal models, human studies and in vitro experiments.

Journal Article Retrovirology · March 16, 2023 Although antiretroviral therapy (ART) has increased life expectancy in people with HIV-1 (PWH), acute and chronic kidney disease remain common in this population and are associated with poor outcomes. A broad spectrum of kidney disorders can be observed in ... Full text Link to item Cite

Tubular-specific expression of HIV protein Vpr leads to severe tubulointerstitial damage accompanied by progressive fibrosis and cystic development.

Journal Article Kidney Int · March 2023 Chronic kidney disease (CKD) is a common cause of morbidity in human immunodeficiency virus (HIV)-positive individuals. HIV infection leads to a wide spectrum of kidney cell damage, including tubular epithelial cell (TEC) injury. Among the HIV-1 proteins, ... Full text Link to item Cite

Establishment, Persistence, and Reactivation of Latent HIV-1 Infection in Renal Epithelial Cells.

Journal Article J Virol · July 27, 2022 HIV-1 persistence in different cell types presents the main obstacle to an HIV-1 cure. We have previously shown that the renal epithelium is a site of HIV-1 infection and that the kidney represents a separate viral compartment from blood. Whether renal cel ... Full text Link to item Cite

Persistent immunogenicity of integrase defective lentiviral vectors delivering membrane-tethered native-like HIV-1 envelope trimers.

Journal Article NPJ Vaccines · April 21, 2022 Integrase Defective Lentiviral Vectors (IDLVs) represent an attractive vaccine platform for delivering HIV-1 antigens, given their ability to induce specific and persistent immune responses in both mice and non-human primates (NHPs). Recent advances in HIV ... Full text Link to item Cite

Safety and efficiency modifications of SIV-based integrase-defective lentiviral vectors for immunization.

Journal Article Mol Ther Methods Clin Dev · December 10, 2021 Integrase-defective lentiviral vectors (IDLVs) represent an attractive platform for vaccine development as a result of the ability to induce persistent humoral- and cellular-mediated immune responses against the encoded transgene. Compared with the parenta ... Full text Link to item Cite

HIV-1 infection of the kidney: mechanisms and implications.

Journal Article AIDS · March 1, 2021 People living with HIV are at higher risk for acute and chronic kidney disease compared with uninfected individuals. Kidney disease in this population is multifactorial, with several contributors including HIV infection of kidney cells, chronic inflammatio ... Full text Link to item Cite

Immunogenicity, safety, and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs.

Journal Article NPJ Vaccines · November 18, 2020 A preventative HIV-1 vaccine is an essential intervention needed to halt the HIV-1 pandemic. Neutralizing antibodies protect against HIV-1 infection in animal models, and thus an approach toward a protective HIV-1 vaccine is to induce broadly cross-reactiv ... Full text Link to item Cite

HIV-1 diversity and compartmentalization in urine, semen, and blood.

Journal Article Medicine (Baltimore) · November 13, 2020 HIV-1 persists indefinitely in multiple cellular reservoirs despite antiretroviral therapy. We previously demonstrated HIV-1 compartmentalization in kidney and urine. Here, we further characterized viruses in urine and when available, compared them to thos ... Full text Link to item Cite

Proliferation of HIV-infected renal epithelial cells following virus acquisition from infected macrophages.

Journal Article AIDS · September 1, 2020 OBJECTIVES: HIV-1 can infect and persist in different organs and tissues, resulting in the generation of multiple viral compartments and reservoirs. Increasing evidence supports the kidney as such a reservoir. Previous work demonstrated that HIV-1 infected ... Full text Link to item Cite

Skeletal Muscle Is an Antigen Reservoir in Integrase-Defective Lentiviral Vector-Induced Long-Term Immunity.

Journal Article Mol Ther Methods Clin Dev · June 12, 2020 We previously developed integrase-defective lentiviral vectors (IDLVs) as an antigen delivery system for inducing strong and prolonged immunity in animal models. Here, we examined the association between persistence of antigen expression and durability of ... Full text Link to item Cite

Call to arms during disruption.

Journal Article J Clin Invest · June 1, 2020 Full text Link to item Cite

Therapeutic vaccination with IDLV-SIV-Gag results in durable viremia control in chronically SHIV-infected macaques.

Journal Article NPJ Vaccines · May 8, 2020 Despite incredible scientific efforts, there is no cure for HIV infection. While antiretroviral treatment (ART) can help control the virus and prevent transmission, it cannot eradicate HIV from viral reservoirs established before the initiation of therapy. ... Full text Link to item Cite

Therapeutic vaccination with IDLV-SIV-Gag results in durable viremia control in chronically SHIV-infected macaques.

Journal Article NPJ Vaccines · 2020 Despite incredible scientific efforts, there is no cure for HIV infection. While antiretroviral treatment (ART) can help control the virus and prevent transmission, it cannot eradicate HIV from viral reservoirs established before the initiation of therapy. ... Full text Link to item Cite

IDLV-HIV-1 Env vaccination in non-human primates induces affinity maturation of antigen-specific memory B cells.

Journal Article Commun Biol · 2018 HIV continues to be a major global health issue. In spite of successful prevention interventions and treatment methods, the development of an HIV vaccine remains a major priority for the field and would be the optimal strategy to prevent new infections. We ... Full text Open Access Link to item Cite

Immunization with an SIV-based IDLV Expressing HIV-1 Env 1086 Clade C Elicits Durable Humoral and Cellular Responses in Rhesus Macaques.

Journal Article Mol Ther · November 2016 The design of an effective HIV-1 vaccine remains a major challenge. Several vaccine strategies based on viral vectors have been evaluated in preclinical and clinical trials, with largely disappointing results. Integrase defective lentiviral vectors (IDLV) ... Full text Open Access Link to item Cite

HIV infection-induced transcriptional program in renal tubular epithelial cells activates a CXCR2-driven CD4+ T-cell chemotactic response.

Journal Article AIDS · July 31, 2016 OBJECTIVE: Viral replication and interstitial inflammation play important roles in the pathogenesis of HIV-associated nephropathy. Cell-cell interactions between renal tubule epithelial cells (RTECs) and HIV-infected T cells can trigger efficient virus int ... Full text Link to item Cite

Identification of HIV-1 genitourinary tract compartmentalization by analyzing the env gene sequences in urine.

Journal Article AIDS · August 24, 2015 OBJECTIVE: HIV-1 persists indefinitely in memory CD4 T cells and other long-lived cellular reservoirs despite antiretroviral therapy. Our group had previously demonstrated that HIV-1 can establish a productive infection in renal epithelial cells and that t ... Full text Link to item Cite

Integrase Defective Lentiviral Vector Promoter Impacts Transgene Expression in Target Cells and Magnitude of Vector-Induced Immune Responses.

Journal Article Viruses · November 14, 2023 Integrase defective lentiviral vectors (IDLVs) are a promising vaccine delivery platform given their ability to induce high magnitude and durable antigen-specific immune responses. IDLVs based on the simian immunodeficiency virus (SIV) are significantly mo ... Full text Link to item Cite

HIV-1 infection of renal epithelial cells: 30 years of evidence from transgenic animal models, human studies and in vitro experiments.

Journal Article Retrovirology · March 16, 2023 Although antiretroviral therapy (ART) has increased life expectancy in people with HIV-1 (PWH), acute and chronic kidney disease remain common in this population and are associated with poor outcomes. A broad spectrum of kidney disorders can be observed in ... Full text Link to item Cite

Tubular-specific expression of HIV protein Vpr leads to severe tubulointerstitial damage accompanied by progressive fibrosis and cystic development.

Journal Article Kidney Int · March 2023 Chronic kidney disease (CKD) is a common cause of morbidity in human immunodeficiency virus (HIV)-positive individuals. HIV infection leads to a wide spectrum of kidney cell damage, including tubular epithelial cell (TEC) injury. Among the HIV-1 proteins, ... Full text Link to item Cite

Establishment, Persistence, and Reactivation of Latent HIV-1 Infection in Renal Epithelial Cells.

Journal Article J Virol · July 27, 2022 HIV-1 persistence in different cell types presents the main obstacle to an HIV-1 cure. We have previously shown that the renal epithelium is a site of HIV-1 infection and that the kidney represents a separate viral compartment from blood. Whether renal cel ... Full text Link to item Cite

Persistent immunogenicity of integrase defective lentiviral vectors delivering membrane-tethered native-like HIV-1 envelope trimers.

Journal Article NPJ Vaccines · April 21, 2022 Integrase Defective Lentiviral Vectors (IDLVs) represent an attractive vaccine platform for delivering HIV-1 antigens, given their ability to induce specific and persistent immune responses in both mice and non-human primates (NHPs). Recent advances in HIV ... Full text Link to item Cite

Safety and efficiency modifications of SIV-based integrase-defective lentiviral vectors for immunization.

Journal Article Mol Ther Methods Clin Dev · December 10, 2021 Integrase-defective lentiviral vectors (IDLVs) represent an attractive platform for vaccine development as a result of the ability to induce persistent humoral- and cellular-mediated immune responses against the encoded transgene. Compared with the parenta ... Full text Link to item Cite

HIV-1 infection of the kidney: mechanisms and implications.

Journal Article AIDS · March 1, 2021 People living with HIV are at higher risk for acute and chronic kidney disease compared with uninfected individuals. Kidney disease in this population is multifactorial, with several contributors including HIV infection of kidney cells, chronic inflammatio ... Full text Link to item Cite

Immunogenicity, safety, and efficacy of sequential immunizations with an SIV-based IDLV expressing CH505 Envs.

Journal Article NPJ Vaccines · November 18, 2020 A preventative HIV-1 vaccine is an essential intervention needed to halt the HIV-1 pandemic. Neutralizing antibodies protect against HIV-1 infection in animal models, and thus an approach toward a protective HIV-1 vaccine is to induce broadly cross-reactiv ... Full text Link to item Cite

HIV-1 diversity and compartmentalization in urine, semen, and blood.

Journal Article Medicine (Baltimore) · November 13, 2020 HIV-1 persists indefinitely in multiple cellular reservoirs despite antiretroviral therapy. We previously demonstrated HIV-1 compartmentalization in kidney and urine. Here, we further characterized viruses in urine and when available, compared them to thos ... Full text Link to item Cite

Proliferation of HIV-infected renal epithelial cells following virus acquisition from infected macrophages.

Journal Article AIDS · September 1, 2020 OBJECTIVES: HIV-1 can infect and persist in different organs and tissues, resulting in the generation of multiple viral compartments and reservoirs. Increasing evidence supports the kidney as such a reservoir. Previous work demonstrated that HIV-1 infected ... Full text Link to item Cite

Skeletal Muscle Is an Antigen Reservoir in Integrase-Defective Lentiviral Vector-Induced Long-Term Immunity.

Journal Article Mol Ther Methods Clin Dev · June 12, 2020 We previously developed integrase-defective lentiviral vectors (IDLVs) as an antigen delivery system for inducing strong and prolonged immunity in animal models. Here, we examined the association between persistence of antigen expression and durability of ... Full text Link to item Cite

Call to arms during disruption.

Journal Article J Clin Invest · June 1, 2020 Full text Link to item Cite

Therapeutic vaccination with IDLV-SIV-Gag results in durable viremia control in chronically SHIV-infected macaques.

Journal Article NPJ Vaccines · May 8, 2020 Despite incredible scientific efforts, there is no cure for HIV infection. While antiretroviral treatment (ART) can help control the virus and prevent transmission, it cannot eradicate HIV from viral reservoirs established before the initiation of therapy. ... Full text Link to item Cite

Therapeutic vaccination with IDLV-SIV-Gag results in durable viremia control in chronically SHIV-infected macaques.

Journal Article NPJ Vaccines · 2020 Despite incredible scientific efforts, there is no cure for HIV infection. While antiretroviral treatment (ART) can help control the virus and prevent transmission, it cannot eradicate HIV from viral reservoirs established before the initiation of therapy. ... Full text Link to item Cite

IDLV-HIV-1 Env vaccination in non-human primates induces affinity maturation of antigen-specific memory B cells.

Journal Article Commun Biol · 2018 HIV continues to be a major global health issue. In spite of successful prevention interventions and treatment methods, the development of an HIV vaccine remains a major priority for the field and would be the optimal strategy to prevent new infections. We ... Full text Open Access Link to item Cite

Immunization with an SIV-based IDLV Expressing HIV-1 Env 1086 Clade C Elicits Durable Humoral and Cellular Responses in Rhesus Macaques.

Journal Article Mol Ther · November 2016 The design of an effective HIV-1 vaccine remains a major challenge. Several vaccine strategies based on viral vectors have been evaluated in preclinical and clinical trials, with largely disappointing results. Integrase defective lentiviral vectors (IDLV) ... Full text Open Access Link to item Cite

HIV infection-induced transcriptional program in renal tubular epithelial cells activates a CXCR2-driven CD4+ T-cell chemotactic response.

Journal Article AIDS · July 31, 2016 OBJECTIVE: Viral replication and interstitial inflammation play important roles in the pathogenesis of HIV-associated nephropathy. Cell-cell interactions between renal tubule epithelial cells (RTECs) and HIV-infected T cells can trigger efficient virus int ... Full text Link to item Cite

Identification of HIV-1 genitourinary tract compartmentalization by analyzing the env gene sequences in urine.

Journal Article AIDS · August 24, 2015 OBJECTIVE: HIV-1 persists indefinitely in memory CD4 T cells and other long-lived cellular reservoirs despite antiretroviral therapy. Our group had previously demonstrated that HIV-1 can establish a productive infection in renal epithelial cells and that t ... Full text Link to item Cite

Murine granulocyte-macrophage colony-stimulating factor expressed from a bicistronic simian immunodeficiency virus-based integrase-defective lentiviral vector does not enhance T-cell responses in mice.

Journal Article Viral Immunol · December 2014 Featured Publication As a prelude to immunization studies in nonhuman primates, we compared in mice the immunogenicity of a simian immunodeficiency virus (SIV)-based integrase (IN)-defective lentiviral vector (IDLV) encoding the model antigen-enhanced green fluorescence protei ... Full text Link to item Cite

Renal epithelial cells produce and spread HIV-1 via T-cell contact.

Journal Article AIDS · October 23, 2014 Featured Publication OBJECTIVES: Increasing evidence supports the role of the kidney as a reservoir for HIV-1. In-vitro co-cultivation of HIV-infected T cells with renal tubule epithelial (RTE) cells results in virus transfer to the latter, whereas cell-free virus infection is ... Full text Link to item Cite

Optimization of mucosal responses after intramuscular immunization with integrase defective lentiviral vector.

Journal Article PLoS One · 2014 Many infectious agents infiltrate the host at the mucosal surfaces and then spread systemically. This implies that an ideal vaccine should induce protective immune responses both at systemic and mucosal sites to counteract invasive mucosal pathogens. We ev ... Full text Link to item Cite

Postintegration HIV-1 infection of cervical epithelial cells mediates contact-dependent productive infection of T cells.

Journal Article J Infect Dis · December 1, 2013 Featured Publication The female genital epithelium plays a protective role against invading pathogens; however, sexual transmission of human immunodeficiency virus type 1 (HIV-1) still occurs in healthy women. To model virus-cell interactions in this barrier during sexual tran ... Full text Link to item Cite

Novel small leucine-rich repeat protein podocan is a negative regulator of migration and proliferation of smooth muscle cells, modulates neointima formation, and is expressed in human atheroma.

Journal Article Circulation · November 26, 2013 Featured Publication BACKGROUND: Smooth muscle cell (SMC) migration and proliferation critically influence the clinical course of vascular disease. We tested the effect of the novel small leucine-rich repeat protein podocan on SMC migration and proliferation using a podocan-de ... Full text Link to item Cite

Career outcomes of the graduates of the American Board of Internal Medicine Research Pathway, 1995-2007.

Journal Article Acad Med · November 2013 Featured Publication PURPOSE: In 1995, the American Board of Internal Medicine (ABIM) formalized an integrated residency curriculum including both clinical and research training (the Research Pathway), designed to develop careers of physician-scientists. Individuals who comple ... Full text Link to item Cite

Simian immunodeficiency virus-Vpx for improving integrase defective lentiviral vector-based vaccines.

Journal Article Retrovirology · August 22, 2012 Featured Publication BACKGROUND: Integrase defective lentiviral vectors (IDLV) represent a promising delivery system for immunization purposes. Human dendritic cells (DC) are the main cell types mediating the immune response and are readily transduced by IDLV, allowing effecti ... Full text Link to item Cite

APOL1 variants increase risk for FSGS and HIVAN but not IgA nephropathy.

Journal Article J Am Soc Nephrol · November 2011 Featured Publication A chromosome 22q13 locus strongly associates with increased risk for idiopathic focal segmental glomerulosclerosis (FSGS), HIV-1-associated nephropathy (HIVAN), and hypertensive ESRD among individuals of African descent. Although initial studies implicated ... Full text Link to item Cite

Prevalence and predictors of proteinuria in HIV-infected and uninfected pregnant women in Cameroon.

Journal Article Nephrol Dial Transplant · September 2011 Featured Publication BACKGROUND: Proteinuria during pregnancy has been associated with increased pregnancy complications. Furthermore, even low-grade proteinuria has been associated with increased mortality in the general population and in non-pregnant HIV-infected women. METH ... Full text Link to item Cite

Virological synapses allow HIV-1 uptake and gene expression in renal tubular epithelial cells.

Journal Article J Am Soc Nephrol · March 2011 Featured Publication In animal models of HIV-associated nephropathy, the expression of HIV regulatory genes in epithelial cells is sufficient to cause disease, but how the CD4-negative epithelial cells come to express HIV genes is unknown. Here, we co-cultured T cells infected ... Full text Link to item Cite

Mucosal human defensins 5 and 6 antagonize the anti-HIV activity of candidate polyanion microbicides.

Journal Article J Innate Immun · 2011 Featured Publication Defensins are highly abundant antimicrobial peptides in the female genital mucosa. We have previously shown that human defensins 5 and 6 (HD5 and HD6), produced by cervicovaginal epithelial cells, significantly enhance HIV infectivity in vitro. Candidate p ... Full text Link to item Cite

Defensins and HIV infection

Journal Article · December 1, 2010 The innate immune system provides the first line of defense against a wide variety of microorganisms before the development of an adaptive immune response. Epithelial cells at mucosal surfaces and recruited leukocytes are often the first to contact microbi ... Full text Cite

Human immunodeficiency virus (HIV)-1 infects human hepatic stellate cells and promotes collagen I and monocyte chemoattractant protein-1 expression: implications for the pathogenesis of HIV/hepatitis C virus-induced liver fibrosis.

Journal Article Hepatology · August 2010 UNLABELLED: Patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) develop more rapid fibrosis than those infected with HCV only. In HIV/HCV-coinfected patients, fibrosis progression correlates with HIV RNA levels, suggesti ... Full text Link to item Cite

Transduction of human antigen-presenting cells with integrase-defective lentiviral vector enables functional expansion of primed antigen-specific CD8(+) T cells.

Journal Article Hum Gene Ther · August 2010 Nonintegrating lentiviral vectors are being developed as a efficient and safe delivery system for both gene therapy and vaccine purposes. Several reports have demonstrated that a single immunization with integration-defective lentiviral vectors (IDLVs) del ... Full text Link to item Cite

Prothymosin-alpha inhibits HIV-1 via Toll-like receptor 4-mediated type I interferon induction.

Journal Article Proc Natl Acad Sci U S A · June 1, 2010 Induction of type I interferons (IFN) is a central feature of innate immune responses to microbial pathogens and is mediated via Toll-like receptor (TLR)-dependent and -independent pathways. Prothymosin-alpha (ProTalpha), a small acidic protein produced an ... Full text Link to item Cite

HIV-1 viral protein r induces ERK and caspase-8-dependent apoptosis in renal tubular epithelial cells.

Journal Article AIDS · May 15, 2010 OBJECTIVE: HIV-associated nephropathy (HIVAN) is the most common cause of end-stage renal disease in persons with HIV/AIDS and is characterized by focal glomerulosclerosis and dysregulated renal tubular epithelial cell (RTEC) proliferation and apoptosis. H ... Full text Link to item Cite

Neisseria gonorrhoeae enhances HIV-1 infection of primary resting CD4+ T cells through TLR2 activation.

Journal Article J Immunol · March 15, 2010 Sexually transmitted infections increase the likelihood of HIV-1 transmission. We investigated the effect of Neisseria gonorrheae (gonococcus [GC]) exposure on HIV replication in primary resting CD4(+) T cells, a major HIV target cell during the early stag ... Full text Link to item Cite

Nonintegrating Lentiviral Vector-Based Vaccine Efficiently Induces Functional and Persistent CD8+ T Cell Responses in Mice.

Journal Article J Biomed Biotechnol · 2010 CD8+ T cells are an essential component of an effective host immune response to tumors and viral infections. Genetic immunization is particularly suitable for inducing CTL responses, because the encoded proteins enter the MHC class I processing pathway thr ... Full text Link to item Cite

FAT10: a novel mediator of Vpr-induced apoptosis in human immunodeficiency virus-associated nephropathy.

Journal Article J Virol · November 2009 Human immunodeficiency virus (HIV)-associated nephropathy is a significant cause of morbidity and mortality in HIV-infected persons. Vpr-induced cell cycle dysregulation and apoptosis of renal tubular epithelial cells are important components of the pathog ... Full text Link to item Cite

Reduction of Stat3 activity attenuates HIV-induced kidney injury.

Journal Article J Am Soc Nephrol · October 2009 HIV-1 Nef induces podocyte proliferation and dedifferentiation by activating the Stat3 and MAPK1,2 pathways. Activation of Stat3 also occurs in human kidneys affected by HIV-associated nephropathy (HIVAN), but its contribution to the development of HIVAN i ... Full text Link to item Cite

HIV-1 Vpr activates the DNA damage response in renal tubule epithelial cells.

Journal Article AIDS · September 24, 2009 HIV-associated nephropathy (HIVAN) is a major cause of HIV-related morbidity and mortality. Pathogenesis involves direct infection of the glomerular and tubular epithelial cells leading to characteristic disorder. Recently, we have shown that HIV-1 Vpr cau ... Full text Link to item Cite

A fine line between molecular umbrella transport and ionophoric activity.

Journal Article Bioconjug Chem · September 2009 A persulfated molecular umbrella derived from one spermine, four lysine, and eight deoxycholic acid molecules was found to exhibit ionophoric activity, as shown by pH discharge and Na(+) and Cl(-) transport experiments. In sharp contrast, a moderately more ... Full text Link to item Cite

Development and use of SIV-based Integrase defective lentiviral vector for immunization.

Journal Article Vaccine · July 23, 2009 Integrase (IN) defective lentiviral vectors have a high safety profile and might prove useful as immunizing agents especially against HIV-1. However, IN defective SIV-based vectors must be developed in order to test their potential in the non-human primate ... Full text Link to item Cite

The differential binding and activity of PRO 2000 against diverse HIV-1 envelopes.

Journal Article J Acquir Immune Defic Syndr · June 1, 2009 OBJECTIVE: PRO 2000 is a polyanionic microbicide that binds directly to the glycoprotein 120 (gp120) envelope protein to inhibit HIV-1 entry. We studied the breadth of PRO 2000 activity against HIV-1 derived from recently transmitted R5 viruses. We also in ... Full text Link to item Cite

The spectrum of kidney disease in patients with AIDS in the era of antiretroviral therapy.

Journal Article Kidney Int · February 2009 With prolonged survival and aging of the HIV-infected population in the era of antiretroviral therapy, biopsy series have found a broad spectrum of HIV-related and co-morbid kidney disease in these patients. Our study describes the variety of renal patholo ... Full text Link to item Cite

Unsung hero Robert C. Gallo.

Journal Article Science · January 9, 2009 Full text Link to item Cite

Conditionally replicating lentiviral-hybrid episomal vectors for suicide gene therapy.

Journal Article Antiviral Res · December 2008 Lentiviral vectors have been shown to be good candidates for gene transfer protocols; however, prevention of insertional mutagenesis remains problematic. Here we report on the design of a conditionally replicating integrase (IN)-defective lentiviral-hybrid ... Full text Link to item Cite

Hepatitis B- and HIV-Related Renal Diseases

Journal Article · December 1, 2008 Full text Cite

HIV-1 Vpr inhibits cytokinesis in human proximal tubule cells.

Journal Article Kidney Int · October 2008 Transgenic mouse models of HIV-associated nephropathy (HIVAN) show that expression of HIV-1 genes in kidney cells produces collapsing focal segmental glomerulosclerosis and microcystic tubular disease typical of the human disease. HIV-1 vpr plays an import ... Full text Link to item Cite

Neisseria gonorrhoeae-induced human defensins 5 and 6 increase HIV infectivity: role in enhanced transmission.

Journal Article J Immunol · May 1, 2008 Sexually transmitted infections (STIs) increase the likelihood of HIV transmission. Defensins are part of the innate mucosal immune response to STIs and therefore we investigated their role in HIV infection. We found that human defensins 5 and 6 (HD5 and H ... Full text Link to item Cite

Inhibitory effect of PRO 2000, a candidate microbicide, on dendritic cell-mediated human immunodeficiency virus transfer.

Journal Article Antimicrob Agents Chemother · May 2008 Without an effective vaccine against human immunodeficiency virus (HIV) infection, topical microbicide development has become a priority. The sulfonated polyanion PRO 2000, a candidate topical microbicide now in phase II/III clinical trials, blocks HIV inf ... Full text Link to item Cite

Human immunodeficiency virus (HIV) infects human arterial smooth muscle cells in vivo and in vitro: implications for the pathogenesis of HIV-mediated vascular disease.

Journal Article Am J Pathol · April 2008 Human immunodeficiency virus (HIV) infection is associated with accelerated atherosclerosis and vasculopathy, although the mechanisms underlying these findings have not been determined. Hypotheses for these observations include: 1) an increase in the preva ... Full text Link to item Cite

SAMMA, a mandelic acid condensation polymer, inhibits dendritic cell-mediated HIV transmission.

Journal Article FEBS Lett · October 2, 2007 SAMMA, a mandelic acid condensation polymer, exhibits a broad antimicrobial activity against several sexually transmitted pathogens including human immunodeficiency virus (HIV). Here we demonstrated that SAMMA suppressed HIV transmission by dendritic cells ... Full text Link to item Cite

Chronic kidney disease in HIV infection: an urban epidemic.

Journal Article AIDS · October 1, 2007 Kidney disease is an important complication of HIV, particularly in minority populations. We describe the burden of chronic kidney disease among 1239 adults followed at an urban AIDS center, with an estimated prevalence of 15.5% (n = 192). Independent pred ... Full text Link to item Cite

alpha-Defensin inhibits influenza virus replication by cell-mediated mechanism(s).

Journal Article J Infect Dis · September 15, 2007 The innate immune system mounts the first host response to pathogens. Because alpha-defensins, which are cationic antimicrobial peptides of polymorphonuclear neutrophils and other leukocytes, are important effectors of the innate immune system, we studied ... Full text Link to item Cite

Influence of prothymosin-alpha on HIV-1 target cells.

Journal Article Ann N Y Acad Sci · September 2007 The important role of CD8(+) T cells in controlling HIV-1 infection through the innate as well as the adaptive immune system is well established. In addition to the major histocompatibility complex (MHC)-dependent cytotoxic activity of CD8(+) T cells, they ... Full text Link to item Cite

Successful immunization with a single injection of non-integrating lentiviral vector.

Journal Article Mol Ther · September 2007 We evaluated the ability of an integrase (IN)-defective self-inactivating lentiviral vector (sinLV) for the delivery of human immunodeficiency virus-1 (HIV-1) envelope sequences in mice to elicit specific immune responses. BALB/c mice were immunized with a ... Full text Link to item Cite

The HIV-positive traveler.

Journal Article Am J Med · July 2007 Antiretroviral therapy has led to a substantial increase in the life expectancy and quality of life for human immunodeficiency virus (HIV)-positive patients. Increasingly, physicians are asked to counsel them before international travel to regions in which ... Full text Link to item Cite

The homophilic adhesion molecule sidekick-1 contributes to augmented podocyte aggregation in HIV-associated nephropathy.

Journal Article FASEB J · May 2007 The collapsing glomerulopathy of HIV-associated nephropathy (HIVAN) is characterized by podocyte dedifferentiation and proliferation. In affected glomeruli, proliferating podocytes adhere in aggregates to form glomerular pseudocrescents and fill an enlarge ... Full text Link to item Cite

Retroviral E-DNA: persistence and gene expression in nondividing immune cells.

Journal Article J Leukoc Biol · November 2006 Following retroviral infection of cells, not only is the proviral DNA integrated into the host genome, but there is also an accumulation of unintegrated extrachromosomal DNA (E-DNA), both linear and circular. Although the integrated DNA is responsible for ... Full text Link to item Cite

ACIDFORM inactivates herpes simplex virus and prevents genital herpes in a mouse model: optimal candidate for microbicide combinations.

Journal Article J Infect Dis · September 15, 2006 The acidic vaginal milieu is presumed to inactivate pathogens but is neutralized by semen. This notion fostered the development of acid-buffering products, such as ACIDFORM (developed by Program for Topical Prevention of Conception and Disease, Rush Univer ... Full text Link to item Cite

Gonococcal lipooligosaccharide suppresses HIV infection in human primary macrophages through induction of innate immunity.

Journal Article J Infect Dis · September 15, 2006 Gonorrhea often occurs as a coinfection with human immunodeficiency virus (HIV). Lipooligosaccharide (LOS) is a component of the gonococcal outer membrane that induces innate immunity through engagement of Toll-like receptor 4 (TLR4). We investigated the e ... Full text Link to item Cite

Novel function of prothymosin alpha as a potent inhibitor of human immunodeficiency virus type 1 gene expression in primary macrophages.

Journal Article J Virol · September 2006 CD8(+) T lymphocytes control human immunodeficiency virus type 1 (HIV-1) infection by a cytotoxic major histocompatibility complex-restricted pathway as well as by secretion of noncytotoxic soluble inhibitory factors. Several components of CD8(+) cell supe ... Full text Link to item Cite

Defensins in innate antiviral immunity.

Journal Article Nat Rev Immunol · June 2006 Defensins are small antimicrobial peptides that are produced by leukocytes and epithelial cells, and that have an important role in innate immunity. Recent advances in understanding the mechanisms of the antiviral action(s) of defensins indicate that they ... Full text Link to item Cite

HIV-1 infection initiates an inflammatory cascade in human renal tubular epithelial cells.

Journal Article J Acquir Immune Defic Syndr · May 2006 HIV-associated nephropathy (HIVAN) is the most common cause of chronic renal failure in HIV-infected patients. Tubulointerstitial inflammation is a prominent component of the histopathology of HIVAN. The pathogenesis of HIVAN is a result of infection of re ... Full text Link to item Cite

Role of ubiquitin-like protein FAT10 in epithelial apoptosis in renal disease.

Journal Article J Am Soc Nephrol · April 2006 Dysregulated apoptosis of renal tubular epithelial cells (RTEC) is an important component of the pathogenesis of several renal diseases, including HIV-associated nephropathy (HIVAN), the most common cause of chronic kidney failure in HIV-infected patients. ... Full text Link to item Cite

Topical microbicides: the time has come.

Journal Article AIDS Read · March 2006 Microbicides are vaginally or rectally applied drugs that inhibit HIV and other sexually transmitted pathogens. About 30 microbicidal products are being studied in preclinical and clinical trials. Data from in vitro, animal, and in vivo investigations with ... Link to item Cite

Kidney and central nervous system as reservoirs of HIV infection.

Journal Article Curr Opin HIV AIDS · March 2006 PURPOSE OF REVIEW: To summarize recent investigations into the establishment and maintenance of the kidney and central nervous system as reservoirs of HIV infection and the resultant pathogenesis of HIV infection in these organs. RECENT FINDINGS: Significa ... Full text Link to item Cite

Dual tropism of HIV-1 envelopes derived from renal tubular epithelial cells of patients with HIV-associated nephropathy.

Journal Article AIDS · February 28, 2006 The phenotype of HIV-1 gp120 envelope derived from renal epithelium and peripheral blood mononuclear cells (PBMC) of patients with HIV-associated nephropathy was investigated in vitro. Chimeric viruses were derived from kidney or blood and used to infect p ... Full text Link to item Cite

Acute renal failure in hospitalized patients with HIV: risk factors and impact on in-hospital mortality.

Journal Article AIDS · February 28, 2006 BACKGROUND: Kidney disease is an increasingly important complication of HIV. OBJECTIVES: To examine the incidence and predictors of acute renal failure before and after the introduction of HAART, and the impact of acute renal failure on in-hospital mortali ... Full text Link to item Cite

PRO 2000 gel inhibits HIV and herpes simplex virus infection following vaginal application: a double-blind placebo-controlled trial.

Journal Article J Infect Dis · January 1, 2006 BACKGROUND: Microbicides used to prevent the transmission of human immunodeficiency virus (HIV) are advancing to clinical trials on the basis of activity observed in vitro and in animal models. However, no data demonstrate activity of microbicides after ap ... Full text Link to item Cite

HIV-1 Nef induces dedifferentiation of podocytes in vivo: a characteristic feature of HIVAN.

Journal Article AIDS · November 18, 2005 OBJECTIVE: To determine the specific role of Nef in the pathogenesis of HIV-associated nephropathy. DESIGN: Podocytes are highly differentiated non-dividing cells in the normal glomerulus, however, they undergo dedifferentiation and acquire a proliferative ... Full text Link to item Cite

Cervicovaginal secretions contribute to innate resistance to herpes simplex virus infection.

Journal Article J Infect Dis · November 15, 2005 Defining and preserving the innate antiviral activity found in cervicovaginal secretions is critical. Cervicovaginal lavage (CVL) samples were obtained from 20 healthy women and evaluated for anti-herpes simplex virus (HSV) activity. CVL samples reduced HS ... Full text Link to item Cite

Candidate sulfonated and sulfated topical microbicides: comparison of anti-human immunodeficiency virus activities and mechanisms of action.

Journal Article Antimicrob Agents Chemother · September 2005 Poly(styrene 4-sulfonate), cellulose sulfate, polymethylenehydroquinone, and PRO 2000 are sulfated or sulfonated polymers (SPs) under development as topical microbicides. They are presumed to work through similar mechanisms of action, although to date ther ... Full text Link to item Cite

Highly active antiretroviral therapy and the epidemic of HIV+ end-stage renal disease.

Journal Article J Am Soc Nephrol · August 2005 The rise in the number of patients with HIV-associated nephropathy and HIV-infection with end-stage renal disease (HIV+ ESRD) continues to be a substantial concern for the ESRD program. In order to assess the impact of highly active antiretroviral therapy ... Full text Link to item Cite

Dual role of alpha-defensin-1 in anti-HIV-1 innate immunity.

Journal Article J Clin Invest · March 2005 Alpha-defensins are abundant antimicrobial peptides in polymorphonuclear leukocytes and play an important role in innate immunity. We have previously shown that alpha-defensin-1 can inhibit HIV-1 replication following viral entry. Here we examined the mole ... Full text Link to item Cite

Nef expressed from human immunodeficiency virus type 1 extrachromosomal DNA downregulates CD4 on primary CD4+ T lymphocytes: implications for integrase inhibitors.

Journal Article J Gen Virol · March 2005 Recently developed integrase inhibitors targeting the HIV-1 integrase (IN) protein block integration of HIV DNA in the target cell, preventing subsequent virus replication. In the absence of integration, viral DNA is shunted towards the formation of extrac ... Full text Link to item Cite

HIV-1 extrachromosomal 2-LTR circular DNA is long-lived in human macrophages.

Journal Article Viral Immunol · 2005 HIV-1 extrachromosomal 2-LTR circles (cc2LTR) are rapidly lost in dividing cell populations and, therefore, might be interpreted as representing new infection and ongoing viral replication. However, recent work demonstrated that cc2LTR persist in infected, ... Full text Link to item Cite

Persulfated molecular umbrellas as anti-HIV and anti-HSV agents.

Journal Article J Am Chem Soc · December 15, 2004 A series of persulfated molecular umbrellas have been synthesized from putrescine, spermidine, spermine, lysine, and cholic acid (1a, 2a, 3a, 4a, and 5a) and their anti-HIV and anti-HSV activities determined. Despite it size, the most active of these conju ... Full text Link to item Cite

Nef stimulates proliferation of glomerular podocytes through activation of Src-dependent Stat3 and MAPK1,2 pathways.

Journal Article J Clin Invest · September 2004 In collapsing focal segmental glomerulosclerosis (FSGS) of HIV-associated nephropathy (HIVAN), podocytes exhibit a high proliferation rate and loss of differentiation markers. We have found previously that the nef gene of HIV-1 is responsible for these cha ... Full text Link to item Cite

Candidate topical microbicides bind herpes simplex virus glycoprotein B and prevent viral entry and cell-to-cell spread.

Journal Article Antimicrob Agents Chemother · June 2004 Topical microbicides designed to prevent acquisition of sexually transmitted infections are urgently needed. Nonoxynol-9, the only commercially available spermicide, damages epithelium and may enhance human immunodeficiency virus transmission. The observat ... Full text Link to item Cite

Renal Manifestations of HIV Infection

Journal Article · April 8, 2004 This chapter discusses renal manifestation of HIV-1 infection, which encompasses a spectrum of disorders and a diversity of clinical syndromes. They are often multifactoral in etiology, but a few very specific diseases are known to be direct consequences o ... Full text Cite

Novel integrase-defective lentiviral episomal vectors for gene transfer.

Journal Article Hum Gene Ther · April 2004 High levels of circular viral extrachromosomal DNA (E-DNA) are normally produced after infection with integration-competent and -incompetent lentiviruses. Although E-DNA has been shown to be transcriptionally active, it lasts for only a short time in repli ... Full text Link to item Cite

Defensins: natural anti-HIV peptides.

Journal Article AIDS Rev · 2004 Mammalian defensins are small cationic antimicrobial peptides predominantly found in leukocytes and epithelial cells engaged in host defense. These peptides act as effector molecules in innate immunity as well as regulators in adaptive immunity. Increasing ... Link to item Cite

Phenotypic characterization of HIV-1 envelopes derived from patients with HIVAN.

Conference JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY · November 1, 2003 Link to item Cite

Podocan, a novel small leucine-rich repeat protein expressed in the sclerotic glomerular lesion of experimental HIV-associated nephropathy.

Journal Article J Biol Chem · August 29, 2003 Growing evidence suggests that human immunodeficiency virus (HIV)-1 infection of podocytes plays a central role in the glomerular disease of HIV-associated nephropathy (HIVAN). As an approach to identify host genes involved in the pathogenesis of the scler ... Full text Link to item Cite

CAF-mediated human immunodeficiency virus (HIV) type 1 transcriptional inhibition is distinct from alpha-defensin-1 HIV inhibition.

Journal Article J Virol · June 2003 CD8(+) T lymphocytes can inhibit human immunodeficiency virus type 1 (HIV-1) replication by secreting a soluble factor(s) known as CD8(+) T-lymphocyte antiviral factor (CAF). One site of CAF action is inhibition of HIV-1 RNA transcription, particularly at ... Full text Link to item Cite

Development of topical microbicides for prevention of human immunodeficiency virus and herpes simplex virus.

Journal Article Am J Reprod Immunol · May 2003 Topical microbicides, designed for vaginal or rectal administration, are needed to prevent human immunodeficiency virus (HIV) and other sexually transmitted infections (STI). Presently marketed topical microbicides are cytotoxic and damage the vaginal epit ... Full text Link to item Cite

Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease.

Journal Article Nat Genet · May 2003 WHIM syndrome is an immunodeficiency disease characterized by neutropenia, hypogammaglobulinemia and extensive human papillomavirus (HPV) infection. Despite the peripheral neutropenia, bone marrow aspirates from affected individuals contain abundant mature ... Full text Link to item Cite

Phosphatidylinositol 3-kinase regulates human immunodeficiency virus type 1 replication following viral entry in primary CD4+ T lymphocytes and macrophages.

Journal Article J Virol · February 2003 Human immunodeficiency virus (HIV) gp120 induces multiple cellular signaling pathways, including the phosphatidylinositol 3-kinase (PI3-kinase) pathway. The role of the PI3-kinase pathway in HIV-1 replication is not understood. Here we examined whether HIV ... Full text Link to item Cite

Mandelic acid condensation polymer: novel candidate microbicide for prevention of human immunodeficiency virus and herpes simplex virus entry.

Journal Article J Virol · November 2002 Presently marketed vaginal barrier methods are cytotoxic and damaging to the vaginal epithelium and natural vaginal flora when used frequently. Novel noncytotoxic agents are needed to protect men and women from sexually transmitted diseases. One novel cand ... Full text Link to item Cite

HIV-1 Nef induces proliferation and anchorage-independent growth in podocytes.

Journal Article J Am Soc Nephrol · July 2002 HIV-associated nephropathy (HIVAN) is now the third leading cause of end-stage renal disease in the African American population. HIV-1 infects renal tubular and glomerular epithelial cells or podocytes, cells that are a critical part of the filtration barr ... Full text Link to item Cite

Replication and compartmentalization of HIV-1 in kidney epithelium of patients with HIV-associated nephropathy.

Journal Article Nat Med · May 2002 HIV-associated nephropathy is a clinicopathologic entity that includes proteinuria, focal segmental glomerulosclerosis often of the collapsing variant, and microcystic tubulointerstitial disease. Increasing evidence supports a role for HIV-1 infection of r ... Full text Link to item Cite

Lentiviral gene transduction of kidney.

Journal Article Hum Gene Ther · February 10, 2002 Gene transfer into kidney holds great potential as a novel therapeutic approach. We have studied the transduction of kidney in vivo after delivery of lentiviral vectors by various routes of administration. A lentiviral vector expressing the bacterial lacZ ... Full text Link to item Cite

Circular viral DNA and anomalous junction sequence in PBMC of HIV-infected individuals with no detectable plasma HIV RNA.

Conference Virology · January 5, 2002 Closed circular (cc) forms of extrachromosomal HIV DNA are detected in patients with high viral loads; however, it is unclear whether these forms remain if virus replication is suppressed to undetectable levels by combination antiretroviral therapy. A nest ... Full text Link to item Cite

A soluble factor(s) secreted from CD8(+) T lymphocytes inhibits human immunodeficiency virus type 1 replication through STAT1 activation.

Journal Article J Virol · January 2002 CD8(+) T lymphocytes can suppress human immunodeficiency virus type 1 (HIV-1) replication by secreting a soluble factor(s) known as CD8(+) T-lymphocyte antiviral factor (CAF). One site of CAF action is inhibition of HIV-1 RNA transcription, particularly at ... Full text Link to item Cite

Polarity of alpha-galactosidase A uptake by renal tubule cells.

Journal Article Kidney Int · January 2002 BACKGROUND: Congenital absence of alpha-galactosidase in Fabry disease leads eventually to renal failure. Fabry disease is an attractive candidate for gene therapy, but uptake mechanisms of the enzyme must be understood for it to be used in treating patien ... Full text Link to item Cite

In vivo gene transfer to kidney by lentiviral vector.

Journal Article Kidney Int · January 2002 BACKGROUND: The growing understanding of the molecular basis of renal diseases makes the development of gene therapy for kidney disorders a potential treatment alternative. Work aimed at determining the feasibility and the efficiency of gene transfer to th ... Full text Link to item Cite

Viral load and CD4 count as predictors of response to hepatitis B vaccine

Journal Article CLINICAL INFECTIOUS DISEASES · October 1, 2001 Link to item Cite

HIV envelope gp120 activates human arterial smooth muscle cells.

Journal Article Proc Natl Acad Sci U S A · August 28, 2001 There have been increasing reports of acute coronary thrombotic events in patients with HIV. Although these clinical events have been attributed primarily to dyslipidemia associated with protease inhibitor therapy, autopsy studies in children with HIV sugg ... Full text Link to item Cite

Development of a novel screen for protease inhibitors.

Journal Article Clin Diagn Lab Immunol · March 2001 We have developed a novel plasmid-based, quantitative, in vitro screen to test the protease-inhibiting activities of existing and newly discovered agents. ... Full text Link to item Cite

Impact of genotypic resistance testing on physician selection of antiretroviral therapy.

Journal Article J Hum Virol · 2001 OBJECTIVES: To determine the impact of genotypic resistance testing on physician selection of antiretroviral therapy. STUDY DESIGN/METHODS: This was a prospective, observational study. A single genotypic resistance test was done when patients failed highly ... Link to item Cite

Renal epithelium is a previously unrecognized site of HIV-1 infection.

Journal Article J Am Soc Nephrol · November 2000 The striking emergence of an epidemic of HIV-related renal disease in patients with end-stage renal disease provided the rationale for the exploration of whether HIV-1 directly infects renal parenchymal cells. Renal glomerular and tubular epithelial cells ... Full text Link to item Cite

Single-dose safety, pharmacology, and antiviral activity of the human immunodeficiency virus (HIV) type 1 entry inhibitor PRO 542 in HIV-infected adults.

Journal Article J Infect Dis · July 2000 PRO 542 (CD4-IgG2) is a recombinant antibody-like fusion protein wherein the Fv portions of both the heavy and light chains of human IgG2 have been replaced with the D1D2 domains of human CD4. Unlike monovalent and divalent CD4-based proteins, tetravalent ... Full text Link to item Cite

Superfibronectin, a multimeric form of fibronectin, increases HIV infection of primary CD4+ T lymphocytes.

Journal Article J Immunol · March 15, 2000 The ability of viruses and bacteria to interact with the extracellular matrix plays an important role in their infectivity and pathogenicity. Fibronectin is a major component of the extracellular matrix in lymph node tissue, the main site of HIV deposition ... Full text Link to item Cite

CD8+ cell lines isolated from HIV-1-infected children have potent soluble HIV-1 inhibitory activity that differs from β-chemokines

Journal Article Viral Immunology · 2000 CD8+ cells from human immunodeficiency virus type 1 (HIV-1) infected individuals have been shown to suppress HIV-1 replication both through a major histocompatibility complex (MHC)-restricted cytolytic pathway as well as through a noncytolytic pathway medi ... Cite

CD8+ cell lines isolated from HIV-1-infected children have potent soluble HIV-1 inhibitory activity that differs from beta-chemokines.

Journal Article Viral Immunol · 2000 CD8+ cells from human immunodeficiency virus type 1 (HIV-1) infected individuals have been shown to suppress HIV-1 replication both through a major histocompatibility complex (MHC)-restricted cytolytic pathway as well as through a noncytolytic pathway medi ... Full text Link to item Cite

Transduction of renal cells in vitro and in vivo by adeno-associated virus gene therapy vectors.

Journal Article J Am Soc Nephrol · September 1999 There has been an increasing interest recently in the possibility of treating renal diseases using gene therapy. The ability to pursue gene therapy for renal diseases has been limited by the availability of an adequate system for gene delivery to the kidne ... Full text Link to item Cite

HIV-associated nephropathy is a late, not early, manifestation of HIV-1 infection.

Journal Article Kidney Int · March 1999 BACKGROUND: Human immunodeficiency virus-associated nephropathy (HIVAN) can be the initial presentation of HIV-1 infection. As a result, many have assumed that HIVAN can occur at any point in the infection. This issue has important implications for appropr ... Full text Link to item Cite

Effect of UV-B phototherapy on plasma HIV type 1 RNA viral level: a self-controlled prospective study.

Journal Article Arch Dermatol · August 1998 OBJECTIVE: To study the plasma human immunodeficiency virus type 1 (HIV-1) RNA levels of 12 patients seropositive for HIV who were undergoing UV-B phototherapy to determine if UV-B phototherapy upregulates HIV activity in humans. DESIGN: A self-controlled ... Full text Link to item Cite

Management of antiretroviral therapy.

Journal Article Semin Nephrol · July 1998 In a very short period of time, availability of antiretroviral drugs has increased from one drug with very modest activity to 12 approved drugs with remarkable potency, particularly when used in combination. The additional availability of absolutely quanti ... Link to item Cite

Sites of recombinant adeno-associated virus integration.

Journal Article Int J Oncol · April 1998 Adeno-associated virus (AAV), a defective parvovirus, is considered a promising vector for the delivery of therapeutic genes to cells. Both wild-type and recombinant AAV display a wide tropism and integrate into the host genome, in the absence of helper vi ... Full text Link to item Cite

Seminars in nephrology

Journal Article Seminars in Nephrology · January 1, 1998 Cite

Adeno-associated virus gene transfer into renal cells: potential for in vivo gene delivery.

Journal Article Exp Nephrol · 1998 The human parvovirus adeno-associated virus (AAV), type 2, has a number of features that make it an attractive choice as a vector for gene delivery to the kidney. AAV vectors permit long-term gene expression in vivo by integration into the host genome, hav ... Full text Link to item Cite

Differential expression of alternatively spliced pX mRNAs in HTLV-I-infected cell lines.

Journal Article Leukemia · June 1997 Human T cell leukemia/lymphotropic virus (HTLV) is a complex 9 kb human retrovirus with at least eight alternatively spliced mRNAs expressed from the 3' or pX region of the genome. These mRNAs allow for the expression of novel proteins from the previously ... Full text Link to item Cite

Adeno-associated viral vectors: background and technical aspects.

Journal Article Exp Nephrol · 1997 There are several obstacles that prevent the successful clinical application of gene therapy. Some of these challenges are unique to the particular disease and organ that is being targeted. Desirable characteristics of approaches aimed at delivery of a the ... Link to item Cite

Molecular therapy for renal diseases.

Journal Article Am J Kidney Dis · October 1996 The introduction of molecular therapy through the delivery of nucleic acids either as oligonucleotides or genetic constructs holds enormous promise for the treatment of renal disease. Significant barriers remain, however, before successful organ-specific m ... Full text Link to item Cite

p53 functional impairment and high p21waf1/cip1 expression in human T-cell lymphotropic/leukemia virus type I-transformed T cells.

Journal Article Blood · September 1, 1996 Human T-cell lymphotropic/leukemia virus type I (HTLV-I) is associated with T-cell transformation both in vivo and in vitro. Although some of the mechanisms responsible for transformation remain unknown, increasing evidence supports a direct role of viral ... Link to item Cite

Patterns of HIV-1 mRNA expression in transgenic mice are tissue-dependent.

Journal Article Virology · August 1, 1994 To explore tissue-specific factors that may be important in HIV-1 transcriptional and post-transcriptional regulation, we examined a transgenic mouse model containing a mutant provirus deleted in the gag and pol region. The level of transgene expression wa ... Full text Link to item Cite

Growth failure and AIDS-like cachexia syndrome in HIV-1 transgenic mice.

Journal Article Virology · May 15, 1994 The mechanisms which predispose to growth failure in infants and children infected with immunodeficiency virus type-1 (HIV-1) are not fully understood. The contributions of viral replication and CD4+ T cell depletion to growth failure in an HIV-1 transgeni ... Full text Link to item Cite

1993 Annual Meeting of the Laboratory of Tumor Cell Biology: Introduction

Journal Article AIDS Research and Human Retroviruses · January 1, 1994 Cite

Increased expression of alpha 4 beta 1 and alpha 5 beta 1 integrins on HTLV-I-infected lymphocytes.

Journal Article Virology · December 1993 T cells interact with the extracellular matrix via integrin receptors and these interactions affect both cellular localization and proliferation. The importance of these interactions in retrovirus-induced diseases, however, remains less clear. In the prese ... Full text Link to item Cite

Inhibition of Rev activity and human immunodeficiency virus type 1 replication by antisense oligodeoxynucleotide phosphorothioate analogs directed against the Rev-responsive element.

Journal Article J Virol · November 1993 The interaction between the Rev protein of human immunodeficiency virus type 1 and its highly structured and conserved RNA target, the Rev-responsive element, is required for virus replication. We demonstrate that antisense oligodeoxynucleotide phosphoroth ... Full text Link to item Cite

HIV-1 infection stimulates T cell invasiveness and synthesis of the 92-kDa type IV collagenase.

Journal Article AIDS Res Hum Retroviruses · June 1993 Tissue-specific localization of HIV-1-infected lymphoid cells may contribute to clinical manifestations of AIDS. Therefore we investigated the effect of HIV-1 infection on mechanisms of T lymphocyte invasion, a process required for movement of cells into a ... Full text Link to item Cite

Identification of a novel cell attachment domain in the HIV-1 Tat protein and its 90-kDa cell surface binding protein.

Journal Article J Biol Chem · March 5, 1993 The HIV-1 transactivator protein Tat is essential for viral gene expression and replication. Tat is taken up by cells and transactivates the HIV-LTR promoter in the cell nucleus. The present studies show that cells adhere to both synthetic and recombinant ... Link to item Cite

Specific inhibition of human immunodeficiency virus type 1 replication by antisense oligonucleotides: an in vitro model for treatment.

Journal Article Proc Natl Acad Sci U S A · December 1, 1992 We have developed a culture system, simulating in vivo conditions of human immunodeficiency virus type 1 (HIV-1) infection, to evaluate the long-term efficacy of antisense oligonucleotide treatment. Five oligonucleotide phosphorothioates (28-mers), complem ... Full text Link to item Cite

Protein isoforms encoded by the pX region of human T-cell leukemia/lymphotropic virus type I.

Journal Article Proc Natl Acad Sci U S A · September 15, 1992 The pX region of the human T-cell leukemia/lymphotropic virus type I (HTLV-I) contains at least four open reading frames (orfI-orfIV). orf III and orf IV encode the regulatory HTLV-I proteins Rex and Tax, which together modulate viral expression, and the p ... Full text Link to item Cite

Prophylactic intravenous amphotericin B in neutropenic autologous bone marrow transplant recipients.

Journal Article J Infect Dis · May 1992 This study assessed the efficacy, toxicity, and pharmacology of low-dose amphotericin B given prophylactically to patients (serum concentrations of 0.2-0.4 microgram/ml) undergoing bone marrow transplantation. Yeast isolates from patients' oropharyngeal ar ... Full text Link to item Cite

Expression of alternatively spliced human T-lymphotropic virus type I pX mRNA in infected cell lines and in primary uncultured cells from patients with adult T-cell leukemia/lymphoma and healthy carriers.

Journal Article Proc Natl Acad Sci U S A · April 1, 1992 Although human T-cell lymphotropic virus type I (HTLV-I) is the etiologic agent of adult T-cell leukemia/lymphoma (ATL), the role of viral gene expression in the progression to and maintenance of the leukemic state in vivo is unclear because of the inabili ... Full text Link to item Cite

Progressive glomerulosclerosis and enhanced renal accumulation of basement membrane components in mice transgenic for human immunodeficiency virus type 1 genes.

Journal Article Proc Natl Acad Sci U S A · March 1, 1992 Patients infected with human immunodeficiency virus type 1 (HIV-1) develop a renal syndrome characterized by proteinuria, renal failure, and focal segmental glomerulosclerosis. By using a noninfectious HIV-1 DNA construct lacking the gag and pol genes, thr ... Full text Link to item Cite

cDNA sequencing confirms HTLV-I expression in adult T-cell leukemia/lymphoma and different sequence variations in vivo and in vitro.

Journal Article Leukemia · 1992 Human T-lymphotropic virus type I (HTLV-I) is the etiological agent of adult T-cell leukemia/lymphoma (ATL) and of tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). In both diseases, expression of viral message can generally only be demo ... Link to item Cite

The promoter of human T-cell leukemia virus type-I is repressed by the immediate-early gene region of human cytomegalovirus in primary blood lymphocytes.

Journal Article Blood · December 1, 1991 Infection with human T-cell leukemia virus type-I (HTLV-1) is associated with a low incidence of morbidity in the form of adult T-cell leukemia as well as neurologic disease, including tropical spastic paraparesis/HTLV-I-associated myelopathy, suggesting t ... Link to item Cite

HIV-1 infection of human T lymphocytes results in enhanced alpha 5 beta 1 integrin expression.

Journal Article J Cell Biol · August 1991 Altered T cell adherence after human immunodeficiency virus 1 (HIV-1) infection may contribute to viral pathogenesis in the acquired immune deficiency syndrome. To address this hypothesis, we assessed mechanisms of T cell adherence to extracellular matrix ... Full text Link to item Cite

Kinetics of expression of multiply spliced RNA in early human immunodeficiency virus type 1 infection of lymphocytes and monocytes.

Journal Article Proc Natl Acad Sci U S A · June 1, 1991 The genome of human immunodeficiency virus type 1 (HIV-1) encodes at least six proteins involved in regulation as well as the structural proteins Gag, Pol, and Env. The interplay of the various regulators generates early and late transcriptional phases in ... Full text Link to item Cite

Amplification of HIV-1 provirus from cerebrospinal fluid and its correlation with neurologic disease.

Journal Article J Infect Dis · June 1990 The polymerase chain reaction (PCR) was used to detect human immunodeficiency virus type 1 (HIV-1) proviral sequences (gag and env) in nucleated cells from the cerebrospinal fluid (CSF) of 31 HIV-1-positive patients, and the results were compared with clin ... Full text Link to item Cite

Trans-activating rev protein of the human immunodeficiency virus 1 interacts directly and specifically with its target RNA.

Journal Article Proc Natl Acad Sci U S A · June 1990 The 20-kDa phosphorylated rev protein from human immunodeficiency virus 1 has been shown to transactivate posttranscriptionally the expression of viral structural proteins by selective stabilization and nuclear export of unspliced and incompletely spliced ... Full text Link to item Cite

Activation of tat-defective human immunodeficiency virus by ultraviolet light.

Journal Article New Biol · May 1990 Ultraviolet light (UV) is known to cause activation of gene expression from the human immunodeficiency virus type 1 (HIV-1) promoter. To address the question of whether tat-defective HIV-1 provirus could be rescued by UV irradiation we examined its effect ... Link to item Cite

Detection of mouse cytomegalovirus nucleic acid in latently infected mice by in vitro enzymatic amplification.

Journal Article J Infect Dis · February 1990 Transmission of human and murine cytomegalovirus (CMV) with transfusions and organ transplantation suggests that the latent virus is located in multiple organs and perhaps multiple cell types. The direct identification and localization of the latent virus ... Full text Link to item Cite

Pseudomonas putrefaciens bacteremia.

Journal Article Rev Infect Dis · 1989 Pseudomonas putrefaciens is an unusual cause of human disease. Since 1978 only five cases of bacteremia due to this organism have been reported. Within 12 recent months four cases of bacteremia due to P. putrefaciens were seen - two occurred in patients wi ... Link to item Cite

Epstein-Barr virus and the elderly host.

Journal Article Rev Infect Dis · 1989 The ability of the Epstein-Barr virus (EBV) to cause latent lifelong infection in the host and its capabilities of transformation may have important implications for the elderly host. Reports in the literature and hospital records were reviewed to determin ... Full text Link to item Cite

High-dose combination cyclophosphamide, cisplatin, and melphalan with autologous bone marrow support. A clinical and pharmacologic study.

Journal Article Cancer Chemother Pharmacol · 1989 A total of 23 patients were treated at five dose escalations with high-dose combination cyclophosphamide, cisplatin, and melphalan with autologous bone marrow support. The maximum tolerated doses of cyclophosphamide, cisplatin, and melphalan were 5,625, 18 ... Full text Link to item Cite

Polymerase chain reaction amplification and in situ hybridization for the detection of human B-lymphotropic virus.

Journal Article J Virol Methods · September 1988 Polymerase chain reaction amplification (PCR) is a recently described technique that allows for the amplification of a given sequence of DNA. It can be used to reliably amplify sequences of up to 3 kb within hours. The amplified sequence can then be recogn ... Full text Link to item Cite

Determinants of the source of cytomegalovirus in murine renal allograft recipients.

Journal Article Transplantation · November 1987 Cytomegalovirus is present in a latent state in renal allografts and may be reactivated in recipients. While human and murine strains are alike in that a primary infection occurs in seronegative recipients of a kidney from a seropositive donor, they may di ... Full text Link to item Cite

Cytomegalovirus pneumonia.

Journal Article Semin Respir Infect · June 1987 Cytomegalovirus (CMV) is a common virus that asymptomatically infects the majority of the population by early adulthood. After initial infection, the virus remains in a latent state in the host and can be reactivated under a variety of conditions. In contr ... Link to item Cite

The source of murine cytomegalovirus in mice receiving kidney allografts.

Journal Article J Infect Dis · December 1985 The sources of cytomegalovirus (CMV) infection in kidney transplant recipients include reactivation of latent endogenous virus in the recipient or reactivation of latent virus in donated blood or kidney. In the present study, kidneys from mice latently inf ... Full text Link to item Cite

Laboratory detection of urinary tract infections

Journal Article Kidney · January 1, 1985 The high incidence of negative urine specimens submitted for microbiologic evaluation (80% in many settings) and the clinical advantages offered by early preliminary results have led to intense efforts over many years to develop rapid, accurate and relativ ... Cite