Scholars@Duke
Stephanie Rachel Jost

Stephanie Rachel Jost

Associate Professor in Surgery
Surgery, Surgical Sciences
stephanie.jost@duke.edu
Duke Research and Discovery @ RTP, Durham, NC 27703
27 Alexandria Way, Durham, NC 27703

Selected Publications

Knockdowns of CD3zeta Chain in Primary NK Cells Illustrate Modulation of Antibody-Dependent Cellular Cytotoxicity Against Human Immunodeficiency Virus-1.

Journal Article AIDS Res Hum Retroviruses · November 2024 Multifaceted natural killer (NK) cell activities are indispensable for controlling human immunodeficiency virus (HIV)-1 transmission and pathogenesis. Among the diverse functions of NK cells, antibody-dependent cellular cytotoxicity (ADCC) has been shown t ... Full text Link to item Cite

NK cells modulate in vivo control of SARS-CoV-2 replication and suppression of lung damage.

Journal Article PLoS Pathog · August 2024 Natural killer (NK) cells play a critical role in virus control. However, it has remained largely unclear whether NK cell mobilization in SARS-CoV-2 infections is beneficial or pathologic. To address this deficit, we employed a validated experimental NK ce ... Full text Link to item Cite

Upregulation of the NKG2D Ligand ULBP2 by JC Polyomavirus Infection Promotes Immune Recognition by Natural Killer Cells.

Journal Article J Infect Dis · June 14, 2024 BACKGROUND: JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML), a potentially fatal complication of severe immune suppression with no effective treatment. Natural killer (NK) cells play critical roles in defense against viral i ... Full text Link to item Cite

Antigen-specific memory NK cell responses against HIV and influenza use the NKG2/HLA-E axis.

Journal Article Sci Immunol · December 8, 2023 Multiple studies have broadened the roles of natural killer (NK) cells functioning as purely innate lymphocytes by demonstrating that they are capable of putative antigen-specific immunological memory against multiple infectious agents including HIV-1 and ... Full text Link to item Cite

Multiplex interrogation of the NK cell signalome reveals global downregulation of CD16 signaling during lentivirus infection through an IL-18/ADAM17-dependent mechanism.

Journal Article PLoS Pathog · September 2023 Despite their importance, natural killer (NK) cell responses are frequently dysfunctional during human immunodeficiency virus-1 (HIV-1) and simian immunodeficiency virus (SIV) infections, even irrespective of antiretroviral therapies, with poorly understoo ... Full text Link to item Cite

NK cell education: Physiological and pathological influences.

Journal Article Front Immunol · 2023 Natural killer (NK) cells represent a critical defense against viral infections and cancers. NK cells require integration of activating and inhibitory NK cell receptors to detect target cells and the balance of these NK cell inputs defines the global NK ce ... Full text Open Access Link to item Cite

Holding back: HLA-associated inhibition of NK cells gives HIV a leg up.

Journal Article Cell Host Microbe · August 10, 2022 In this issue of Cell Host & Microbe, Li et al. unveil an association between HLA-B∗46:01 and HIV disease progression in Asian populations. The distinct natural killer (NK) cell signature identified in individuals carrying HLA-B∗46:01 strongly suggests tha ... Full text Link to item Cite

Learning to Be Elite: Lessons From HIV-1 Controllers and Animal Models on Trained Innate Immunity and Virus Suppression.

Journal Article Front Immunol · 2022 Although antiretroviral therapy (ART) has drastically changed the lives of people living with human immunodeficiency virus-1 (HIV-1), long-term treatment has been associated with a vast array of comorbidities. Therefore, a cure for HIV-1 remains the best o ... Full text Link to item Cite

A Genome-Wide CRISPR/Cas9-Based Screen Identifies Heparan Sulfate Proteoglycans as Ligands of Killer-Cell Immunoglobulin-Like Receptors.

Journal Article Front Immunol · 2021 While human leukocyte antigen (HLA) and HLA-like proteins comprise an overwhelming majority of known ligands for NK-cell receptors, the interactions of NK-cell receptors with non-conventional ligands, particularly carbohydrate antigens, is less well descri ... Full text Open Access Link to item Cite

Brief Report: Decreased JC Virus-Specific Antibody-Dependent Cellular Cytotoxicity in HIV-Seropositive PML Survivors.

Journal Article J Acquir Immune Defic Syndr · October 1, 2019 BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is an often fatal disease caused by JC virus (JCV) in severely immunocompromised patients, including HIV patients. Development of therapeutics to prevent or treat PML is an urgent medical need. W ... Full text Link to item Cite

Semaphorin 7A modulates cytokine-induced memory-like responses by human natural killer cells.

Journal Article Eur J Immunol · August 2019 Cytokine-induced memory-like (CIML) NK cells are endowed with the capacity to mediate enhanced effector functions upon cytokine or activating receptor restimulation for several weeks following short-term preactivation with IL-12, IL-15, and IL-18. Promisin ... Full text Link to item Cite

A Natural Impact: NK Cells at the Intersection of Cancer and HIV Disease.

Journal Article Front Immunol · 2019 Despite efficient suppression of plasma viremia in people living with HIV (PLWH) on cART, evidence of HIV-induced immunosuppression remains, and normally benign and opportunistic pathogens become major sources of co-morbidities, including virus-induced can ... Full text Open Access Link to item Cite

NK Cells Contribute to the Immune Risk Profile in Kidney Transplant Candidates.

Journal Article Front Immunol · 2019 Background: A previously proposed immune risk profile (IRP), based on T cell phenotype and CMV serotype, is associated with mortality in the elderly and increased infections post-kidney transplant. To evaluate if NK cells contribute to the IRP and if the I ... Full text Open Access Link to item Cite

Progressive lentivirus infection induces natural killer cell receptor-expressing B cells in the gastrointestinal tract.

Journal Article AIDS · July 31, 2018 OBJECTIVE: Recently, a seemingly novel innate immune cell subset bearing features of natural killer and B cells was identified in mice. So-called NKB cells appear as first responders to infections, but whether this cell population is truly novel or is in f ... Full text Link to item Cite

NK-cell activation is associated with increased HIV transcriptional activity following allogeneic hematopoietic cell transplantation.

Journal Article Blood Adv · June 26, 2018 Graft-versus-host effects may lead to HIV-1 reactivation and cell death of infected pre-HCT CD4+ T cells. Natural killer cell activation correlates with in vitro HIV-1 transcriptional activity in the setting of HCT. ... Full text Link to item Cite

Human Herpes Virus 8 in HIV-1 infected individuals receiving cancer chemotherapy and stem cell transplantation.

Journal Article PLoS One · 2018 BACKGROUND: Human Herpes Virus 8 (HHV8) can cause Kaposi's Sarcoma (KS) in immunosuppressed individuals. However, little is known about the association between chemotherapy or hematopoietic stem cell transplantation (HSCT), circulating HHV8 DNA levels, and ... Full text Open Access Link to item Cite

Human Immunodeficiency Virus Type 1 Persistence Following Systemic Chemotherapy for Malignancy.

Journal Article J Infect Dis · July 15, 2017 BACKGROUND: Systemic chemotherapies for various malignancies have been shown to significantly, yet transiently, decrease numbers of CD4+ T lymphocytes, a major reservoir for human immunodeficiency virus type 1 (HIV-1) infection. However, little is known ab ... Full text Open Access Link to item Cite

HIV-1-Mediated Downmodulation of HLA-C Impacts Target Cell Recognition and Antiviral Activity of NK Cells.

Journal Article Cell Host Microbe · July 12, 2017 It was widely accepted that HIV-1 downregulates HLA-A/B to avoid CTL recognition while leaving HLA-C unaltered in order to prevent NK cell activation by engaging inhibitory NK cell receptors, but it was recently observed that most primary isolates of HIV-1 ... Full text Link to item Cite

Open conformers of HLA-F are high-affinity ligands of the activating NK-cell receptor KIR3DS1.

Journal Article Nat Immunol · September 2016 The activating natural killer (NK)-cell receptor KIR3DS1 has been linked to the outcome of various human diseases, including delayed progression of disease caused by human immunodeficiency virus type 1 (HIV-1), yet a ligand that would account for its biolo ... Full text Link to item Cite

CCR5-Δ32 Heterozygosity, HIV-1 Reservoir Size, and Lymphocyte Activation in Individuals Receiving Long-term Suppressive Antiretroviral Therapy.

Journal Article J Infect Dis · March 1, 2016 We conducted a case-controlled study of the associations of CCR5-Δ32 heterozygosity with human immunodeficiency virus type 1 (HIV-1) reservoir size, lymphocyte activation, and CCR5 expression in 114 CCR5(Δ32/WT) and 177 wild-type CCR5 AIDS Clinical Trials ... Full text Open Access Link to item Cite

Naturally Occurring Subclinical Endotoxemia in Humans Alters Adaptive and Innate Immune Functions through Reduced MAPK and Increased STAT1 Phosphorylation.

Journal Article J Immunol · January 15, 2016 Multiple studies have shown correlates of immune activation with microbial translocation and plasma LPS during HIV infection. It is unclear whether this activation is due to LPS, residual viral replication, or both. Few studies have addressed the effects o ... Full text Link to item Cite

Increased frequencies of CD8+CD57+ T cells are associated with antibody neutralization breadth against HIV in viraemic controllers.

Journal Article J Int AIDS Soc · 2016 INTRODUCTION: An effective prophylactic vaccine against HIV will need to elicit antibody responses capable of recognizing and neutralizing rapidly evolving antigenic regions. The immunologic milieu associated with development of neutralizing antibody bread ... Full text Link to item Cite

Antigen-specific NK cell memory in rhesus macaques.

Journal Article Nat Immunol · September 2015 Natural killer (NK) cells have traditionally been considered nonspecific components of innate immunity, but recent studies have shown features of antigen-specific memory in mouse NK cells. However, it has remained unclear whether this phenomenon also exist ... Full text Link to item Cite

Influence of Glycosylation Inhibition on the Binding of KIR3DL1 to HLA-B*57:01.

Journal Article PLoS One · 2015 Viral infections can affect the glycosylation pattern of glycoproteins involved in antiviral immunity. Given the importance of protein glycosylation for immune function, we investigated the effect that modulation of the highly conserved HLA class I N-glyca ... Full text Open Access Link to item Cite

Increased frequency and function of KIR2DL1-3⁺ NK cells in primary HIV-1 infection are determined by HLA-C group haplotypes.

Journal Article Eur J Immunol · October 2014 The acquisition and maintenance of NK-cell function is mediated by inhibitory killer-cell immunoglobulin-like receptors (KIRs) through their interaction with HLA class I molecules. Recently, HLA-C expression levels were shown to be correlated with protecti ... Full text Link to item Cite

Enhanced immune activation linked to endotoxemia in HIV-1 seronegative MSM.

Journal Article AIDS · September 10, 2014 This study assessed cellular and soluble markers of immune activation in HIV-1 seronegative MSM. MSM immune profiles were characterized by an increased expression of CD57 on T cells and endotoxemia. Endotoxin presence was linked to recent high-risk exposur ... Full text Open Access Link to item Cite

CD4+ T-cell help enhances NK cell function following therapeutic HIV-1 vaccination.

Journal Article J Virol · August 2014 UNLABELLED: Increasing data suggest that NK cells can mediate antiviral activity in HIV-1-infected humans, and as such, novel approaches harnessing the anti-HIV-1 function of both T cells and NK cells represent attractive options to improve future HIV-1 im ... Full text Link to item Cite

Dysregulated Tim-3 expression on natural killer cells is associated with increased Galectin-9 levels in HIV-1 infection.

Journal Article Retrovirology · July 18, 2013 BACKGROUND: Natural killer (NK) cells constitutively express high levels of Tim-3, an immunoregulatory molecule recently proposed to be a marker for mature and functional NK cells. Whether HIV-1 infection modulates the expression of Tim-3 on NK cells, or t ... Full text Link to item Cite

Lessons from Viral Superinfections for HIV-1 Vaccine Design

Journal Article Journal of AIDS & Clinical Research · 2013 Full text Open Access Cite

Control of human viral infections by natural killer cells.

Journal Article Annu Rev Immunol · 2013 Natural killer (NK) cells are effector cells of the innate immune system and are important in the control of viral infections. Their relevance is reflected by the multiple mechanisms evolved by viruses to evade NK cell-mediated immune responses. Over recen ... Full text Link to item Cite

Evasion from NK cell-mediated immune responses by HIV-1.

Journal Article Microbes Infect · September 2012 Human immunodeficiency virus type 1 (HIV-1) mostly owes its success to its ability to evade host immune responses. Understanding viral immune escape mechanisms is a prerequisite to improve future HIV-1 vaccine design. This review focuses on the strategies ... Full text Link to item Cite

Harnessing innate and adaptive immunity for viral vaccine design.

Journal Article Expert Rev Vaccines · July 2012 The recent Keystone Symposia meeting on HIV Vaccines was held on 21-26 March 2012 in Keystone (CO, USA) back-to-back with the Viral Immunity meeting, creating synergy between the two areas of research. In this short report of the meeting, the authors will ... Full text Link to item Cite

Reduced frequencies of NKp30+NKp46+, CD161+, and NKG2D+ NK cells in acute HCV infection may predict viral clearance.

Journal Article J Hepatol · August 2011 BACKGROUND & AIMS: While the majority of HCV-infected patients progress to chronic hepatitis, a small fraction of individuals are able to clear the virus. Resolution of infection occurs within the first few weeks to months of infection, suggesting that inn ... Full text Link to item Cite

Expansion of 2B4+ natural killer (NK) cells and decrease in NKp46+ NK cells in response to influenza.

Journal Article Immunology · April 2011 Several studies have highlighted the importance of murine natural killer (NK) cells in the control of influenza virus infection, notably through the natural cytotoxicity receptor NKp46. However, little is known about the involvement of NK cells in human in ... Full text Link to item Cite

A robust, high-throughput assay to determine the phagocytic activity of clinical antibody samples.

Journal Article J Immunol Methods · March 7, 2011 Phagocytosis can be induced via the engagement of Fcγ receptors by antibody-opsonized material. Furthermore, the efficiency of antibody-induced effector functions has been shown to be dramatically modulated by changes in antibody glycosylation. Because inf ... Full text Link to item Cite

Changes in cytokine levels and NK cell activation associated with influenza.

Journal Article PLoS One · 2011 Several studies have highlighted the important role played by murine natural killer (NK) cells in the control of influenza infection. However, human NK cell responses in acute influenza infection, including infection with the 2009 pandemic H1N1 influenza v ... Full text Link to item Cite

MHC class I chain-related protein A shedding in chronic HIV-1 infection is associated with profound NK cell dysfunction.

Journal Article Virology · October 10, 2010 Natural killer (NK) cells play a critical role in host defense against viral infections. However chronic HIV-1 infection is associated with an accumulation of dysfunctional NK cells, that poorly control viral replication. The underlying mechanisms for this ... Full text Open Access Link to item Cite

Matrix metalloprotease inhibitors restore impaired NK cell-mediated antibody-dependent cellular cytotoxicity in human immunodeficiency virus type 1 infection.

Journal Article J Virol · September 2009 Increasing evidence suggests that NK cells not only are critical in the initial host defense against pathogens but also may contribute to continued protection from human immunodeficiency virus type 1 (HIV-1) disease progression. NK cell cytolysis can be in ... Full text Link to item Cite

APOBEC3-independent interferon-induced viral clearance in hepatitis B virus transgenic mice.

Journal Article J Virol · July 2008 Interferon (IFN) has been part of the standard treatment of chronic hepatitis B infection for more than 2 decades, yet the mechanism of action of this antiviral remains poorly understood. It was recently observed that members of the human APOBEC family of ... Full text Link to item Cite

Induction of antiviral cytidine deaminases does not explain the inhibition of hepatitis B virus replication by interferons.

Journal Article J Virol · October 2007 Interferons (IFNs) play a major role in the control of hepatitis B virus (HBV), whether as endogenous cytokines limiting the spread of the virus during the acute phase of the infection or as drugs for the treatment of its chronic phase. However, the mechan ... Full text Link to item Cite

HIV-1 co/super-infection in intravenous drug users.

Journal Article AIDS · July 2, 2004 BACKGROUND: The frequency of HIV-1 co/super-infection is unknown despite their implications for public health and vaccine development. This issue was addressed during an epidemic of both CRF11 and B subtype among intravenous drug users (IVDUs). METHODS: Bu ... Full text Link to item Cite

Infrequent transmission of HIV-1 drug-resistant variants.

Journal Article Antivir Ther · June 2004 Transmission of drug-resistant variants is influenced by several factors, including the prevalence of drug resistance in the population of HIV-1-infected patients, HIV-1 RNA levels and transmission by recently infected patients. In order to evaluate the im ... Link to item Cite

A patient with HIV-1 superinfection.

Journal Article N Engl J Med · September 5, 2002 Full text Link to item Cite