Scholars@Duke
David James Pickup

David James Pickup

Associate Professor Emeritus of Molecular Genetics and Microbiology
Molecular Genetics and Microbiology
Duke Box 3020, Durham, NC 27710
321 Highlands Bluffs Drive, Cary, NC 27518

Selected Publications

Recombinant MVA-prime elicits neutralizing antibody responses by inducing antigen-specific B cells in the germinal center

Conference Npj Vaccines · December 1, 2021 The RV144 HIV-1 vaccine trial has been the only clinical trial to date that has shown any degree of efficacy and associated with the presence of vaccine-elicited HIV-1 envelope-specific binding antibody and CD4+ T-cell responses. This trial also showed tha ... Full text Cite

Optimized Mucosal Modified Vaccinia Virus Ankara Prime/Soluble gp120 Boost HIV Vaccination Regimen Induces Antibody Responses Similar to Those of an Intramuscular Regimen.

Journal Article J Virol · July 15, 2019 The benefits of mucosal vaccines over injected vaccines are difficult to ascertain, since mucosally administered vaccines often induce serum antibody responses of lower magnitude than those induced by injected vaccines. This study aimed to determine if muc ... Full text Link to item Cite

Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques.

Journal Article mSphere · 2018 Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) contributes to an estimated 150,000 new infections annually. Maternal vaccination has proven safe and effective at mitigating the impact of other neonatal pathogens and is o ... Full text Open Access Link to item Cite

Impact of Poxvirus Vector Priming, Protein Coadministration, and Vaccine Intervals on HIV gp120 Vaccine-Elicited Antibody Magnitude and Function in Infant Macaques.

Journal Article Clin Vaccine Immunol · October 2017 Despite success in reducing vertical HIV transmission by maternal antiretroviral therapy, several obstacles limit its efficacy during breastfeeding, and breast-milk transmission is now the dominant mode of mother-to-child transmission (MTCT) of HIV in infa ... Full text Link to item Cite

Modified Vaccinia Ankara Virus Vaccination Provides Long-Term Protection against Nasal Rabbitpox Virus Challenge.

Journal Article Clin Vaccine Immunol · July 2016 Modified vaccinia Ankara virus (MVA) is a smallpox vaccine candidate. This study was performed to determine if MVA vaccination provides long-term protection against rabbitpox virus (RPXV) challenge, an animal model of smallpox. Two doses of MVA provided 10 ... Full text Link to item Cite

Combined HIV-1 Envelope Systemic and Mucosal Immunization of Lactating Rhesus Monkeys Induces a Robust Immunoglobulin A Isotype B Cell Response in Breast Milk.

Journal Article J Virol · May 15, 2016 UNLABELLED: Maternal vaccination to induce anti-HIV immune factors in breast milk is a potential intervention to prevent postnatal HIV-1 mother-to-child transmission (MTCT). We previously demonstrated that immunization of lactating rhesus monkeys with a mo ... Full text Open Access Link to item Cite

Poxviruses

Other In: Encyclopedia of Life Sciences (eLS). · 2015 Full text Cite

T cell inactivation by poxviral B22 family proteins increases viral virulence.

Journal Article PLoS Pathog · May 2014 Infections with monkeypox, cowpox and weaponized variola virus remain a threat to the increasingly unvaccinated human population, but little is known about their mechanisms of virulence and immune evasion. We now demonstrate that B22 proteins, encoded by t ... Full text Link to item Cite

Mucosal immunization of lactating female rhesus monkeys with a transmitted/founder HIV-1 envelope induces strong Env-specific IgA antibody responses in breast milk.

Journal Article J Virol · June 2013 We previously demonstrated that vaccination of lactating rhesus monkeys with a DNA prime/vector boost strategy induces strong T-cell responses but limited envelope (Env)-specific humoral responses in breast milk. To improve vaccine-elicited antibody respon ... Full text Link to item Cite

Production of prostaglandin E₂ in response to infection with modified vaccinia Ankara virus.

Journal Article Virology · July 5, 2012 Prostaglandin E₂ (PGE₂) is an arachidonic acid (AA)-derived signaling molecule that can influence host immune responses to infection or vaccination. In this study, we investigated PGE₂ production in vitro by cells infected with the poxvirus vaccine strain, ... Full text Link to item Cite

Cowpox virus induces interleukin-10 both in vitro and in vivo.

Journal Article Virology · August 15, 2011 Cowpox virus infection induces interleukin-10 (IL-10) production from mouse bone marrow-derived dendritic cells (BMDCs) or cells of the mouse macrophage line (RAW264.7) at about 1800 pg/ml, whereas infections with vaccinia virus (strains WR or MVA) induced ... Full text Link to item Cite

Cowpox virus inhibits human dendritic cell immune function by nonlethal, nonproductive infection.

Journal Article Virology · April 10, 2011 Orthopoxviruses encode multiple proteins that modulate host immune responses. We determined whether cowpox virus (CPXV), a representative orthopoxvirus, modulated innate and acquired immune functions of human primary myeloid DCs and plasmacytoid DCs and mo ... Full text Link to item Cite

Cell biology. Propelling progeny.

Journal Article Science · February 12, 2010 Full text Link to item Cite

Two mechanistically distinct immune evasion proteins of cowpox virus combine to avoid antiviral CD8 T cells.

Journal Article Cell Host Microbe · November 19, 2009 Featured Publication Downregulation of MHC class I on the cell surface is an immune evasion mechanism shared by many DNA viruses, including cowpox virus. Previously, a cowpox virus protein, CPXV203, was shown to downregulate MHC class I. Here we report that CPXV12 is the only ... Full text Link to item Cite

Modified vaccinia virus Ankara can activate NF-kappaB transcription factors through a double-stranded RNA-activated protein kinase (PKR)-dependent pathway during the early phase of virus replication.

Journal Article Virology · September 1, 2009 Featured Publication Modified vaccinia virus Ankara (MVA), which is a promising replication-defective vaccine vector, is unusual among the orthopoxviruses in activating NF-kappaB transcription factors in cells of several types. In human embryonic kidney (HEK 293T) cells, the M ... Full text Link to item Cite

Vaccination with Venezuelan equine encephalitis replicons encoding cowpox virus structural proteins protects mice from intranasal cowpox virus challenge.

Journal Article Virology · June 5, 2007 Featured Publication An anti-poxvirus vaccine based on replicon particles of Venezuelan equine encephalitis virus (VRP) is being developed. The cowpox virus genes encoding structural proteins corresponding to vaccinia virus proteins A33, B5, and A27 were each expressed from VR ... Full text Link to item Cite

Understanding orthopoxvirus interference with host immune responses to inform novel vaccine design.

Journal Article Expert Rev Vaccines · February 2007 Featured Publication Jenner's original vaccine used cowpox virus. Cowpox virus and, subsequently, vaccinia virus, a closely related Orthopoxvirus, provided the means to eradicate smallpox. This history and the unique properties of the virus suggest that vaccinia virus will con ... Full text Link to item Cite

Post-transcription cleavage generates the 3' end of F17R transcripts in vaccinia virus.

Journal Article Virology · February 5, 2004 Featured Publication Most vaccinia virus intermediate and late mRNAs possess 3' ends that are extremely heterogeneous in sequence. However, late mRNAs encoding the cowpox A-type inclusion protein (ATI), the second largest subunit of the RNA polymerase, and the late telomeric t ... Full text Link to item Cite

Identification of the orthopoxvirus p4c gene, which encodes a structural protein that directs intracellular mature virus particles into A-type inclusions.

Journal Article J Virol · November 2002 Featured Publication The orthopoxvirus gene p4c has been identified in the genome of the vaccinia virus strain Western Reserve. This gene encodes the 58-kDa structural protein P4c present on the surfaces of the intracellular mature virus (IMV) particles. The gene is disrupted ... Full text Link to item Cite

Cowpox virus encodes a fifth member of the tumor necrosis factor receptor family: a soluble, secreted CD30 homologue.

Journal Article Proc Natl Acad Sci U S A · June 11, 2002 Featured Publication Cowpox virus (Brighton Red strain) possesses one of the largest genomes in the Orthopoxvirus genus. Sequence analysis of a region of the genome that is type-specific for cowpox virus identified a gene, vCD30, encoding a soluble, secreted protein that is th ... Full text Link to item Cite

Cowpox virus and other members of the orthopoxvirus genus interfere with the regulation of NF-kappaB activation.

Journal Article Virology · September 15, 2001 Featured Publication NF-kappaB comprises a family of transcription factors that regulate key immune processes. In this study, the effects of orthopoxvirus infection upon the activation of NF-kappaB were examined. During the early phase of infection, cowpox virus can inhibit th ... Full text Link to item Cite

A 43-nucleotide RNA cis-acting element governs the site-specific formation of the 3' end of a poxvirus late mRNA.

Journal Article Virology · March 1, 1999 Featured Publication The 3' ends of late mRNAs of the ati gene, encoding the major component of the A-type inclusions, are generated by endoribonucleolytic cleavage at a specific site in the primary transcript [Antczak et al., (1992), Proc. Natl. Acad. Sci. USA 89, 12033-12037 ... Full text Link to item Cite

A third distinct tumor necrosis factor receptor of orthopoxviruses.

Journal Article Proc Natl Acad Sci U S A · March 31, 1998 Featured Publication Cowpox virus Brighton red strain (CPV) contains a gene, crmD, which encodes a 320-aa tumor necrosis factor receptor (TNFR) of 44% and 22% identity, respectively, to the CPV TNFR-like proteins, cytokine response modifiers (crm) CrmB and CrmC. The crmD gene ... Full text Link to item Cite

Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits beta chemokine activity yet lacks sequence homology to known chemokine receptors.

Journal Article Virology · September 29, 1997 Featured Publication Poxvirus genomes encode several proteins which inhibit specific elements of the host immune response. We show the "35K" virulence gene in variola and cowpox viruses, whose vaccinia and Shope fibroma virus equivalents are strongly conserved in sequence, act ... Full text Link to item Cite

Cowpox virus genome encodes a second soluble homologue of cellular TNF receptors, distinct from CrmB, that binds TNF but not LT alpha.

Journal Article Virology · September 1, 1996 Featured Publication We show the cowpox genome (Brighton Red strain) contains a single copy gene, crmC, expressed at late times during viral infection, encoding a soluble, secreted protein whose sequence marks it as a new member of the TNF receptor family. The cysteine-rich pr ... Full text Link to item Cite

Proteolytic activation of the cell death protease Yama/CPP32 by granzyme B.

Journal Article Proc Natl Acad Sci U S A · March 5, 1996 Featured Publication The serine protease granzyme B, which is secreted by cytotoxic cells, is one of the major effectors of apoptosis in susceptible targets. To examine the apoptotic mechanism of granzyme B, we have analyzed its effect on purified proteins that are thought to ... Full text Link to item Cite

The mode of death of pig kidney cells infected with cowpox virus is governed by the expression of the crmA gene.

Journal Article Virology · March 1, 1996 Pig kidney cells (LLC-PK1) were infected with one of three viruses: wild-type cowpox virus (Brighton red strain) expressing the crmA gene; recombinant cowpox virus A602, lacking the crmA gene; or cowpox virus A604, a revertant of virus A602, expressing the ... Full text Link to item Cite

Granzyme B is inhibited by the cowpox virus serpin cytokine response modifier A.

Journal Article J Biol Chem · May 5, 1995 The ability of cytolytic cells to cause apoptosis in target cells is in part due to the action of the serine proteinase granzyme B. We demonstrate that granzyme B is inhibited, with an association rate constant of 2.9 x 10(5) M-1 s-1, by the cowpox viral s ... Full text Link to item Cite

Human IL-1 beta processing and secretion in recombinant baculovirus-infected Sf9 cells is blocked by the cowpox virus serpin crmA.

Journal Article J Immunol · March 1, 1995 Biologically active, mature IL-1 beta (mIL-1 beta) is released from activated monocytes after proteolytic processing from an inactive precursor (pIL-1 beta). IL-1 beta converting enzyme (ICE), the first member of a newly discovered family of cysteine prote ... Link to item Cite

Cowpox virus contains two copies of an early gene encoding a soluble secreted form of the type II TNF receptor.

Journal Article Virology · October 1994 Featured Publication The inverted terminal repeats of the DNA of cowpox virus (Brighton Red strain) contain the crmB gene, an additional member of a family of viral genes that modify cytokine responses to infection. The crmB gene is transcribed from an early promoter. The prim ... Full text Link to item Cite

Inhibition of interleukin-1 beta converting enzyme by the cowpox virus serpin CrmA. An example of cross-class inhibition.

Journal Article J Biol Chem · July 29, 1994 We reported previously that human interleukin-1 beta converting enzyme (ICE) is regulated by the CrmA serpin encoded by cowpox virus. We now report the mechanism and kinetics of this unusual inhibition of a cysteine proteinase by a member of the serpin sup ... Link to item Cite

Poxviral modifiers of cytokine responses to infection.

Journal Article Infect Agents Dis · 1994 Poxviruses include some of the most virulent of all human pathogens. In part, the virulence of these viruses stems from their abilities to counter host defenses against infection. A family of cytokine-response modifiers encoded by the poxviruses contribute ... Link to item Cite

In Vitro Expression of Serpins

Conference · January 1, 1994 This chapter describes the in vitro expression of serpins. All serpins do not inhibit proteinases but those that do show a distinctive unfolding tendency at relatively low denaturant concentration. Upon cleavage in the reactive site loop (RSL), the conform ... Full text Cite

SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTORS OF 2 TYPES ARE ENCODED BY COWPOX VIRUS

Conference JOURNAL OF CELLULAR BIOCHEMISTRY · January 26, 1993 Link to item Cite

Site-specific RNA cleavage generates the 3' end of a poxvirus late mRNA.

Journal Article Proc Natl Acad Sci U S A · December 15, 1992 Featured Publication The cowpox virus late mRNAs encoding the major protein of the A-type inclusions have 3' ends corresponding to a single site in the DNA template. The DNA sequence of the Alu I-Xba I fragment at this position encodes an RNA cis-acting signal, designated the ... Full text Link to item Cite

Vaccinia and cowpox viruses encode a novel secreted interleukin-1-binding protein.

Journal Article Cell · October 2, 1992 Featured Publication Supernatants from vaccinia virus (VV)-infected CV-1 cells were examined and found to contain a 33 kd protein capable of binding murine interleukin-1 beta (mIL-1 beta). A VV open reading frame (ORF) that exhibits 30% amino acid identity to the type II IL-1 ... Full text Link to item Cite

The eukaryotic translation initiation factor 4E is not modified during the course of vaccinia virus replication.

Journal Article Virology · June 1992 The ability of vaccinia virus to inhibit processes of cap-dependent translational initiation by inactivating the eukaryotic translation initiation factor 4E (eIF-4E) has been examined. Analyses of the quantities of eIF-4E present in either uninfected mouse ... Full text Link to item Cite

Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme.

Journal Article Cell · May 15, 1992 Featured Publication Cowpox virus effectively inhibits inflammatory responses against viral infection in the chick embryo. This study demonstrates that one of the viral genes necessary for this inhibition, the crmA gene (a cytokine response modifier gene), encodes a serpin tha ... Full text Link to item Cite

Transcription of the terminal loop region of vaccinia virus DNA is initiated from the telomere sequences directing DNA resolution.

Journal Article Virology · April 1991 The telomeres of vaccinia virus DNA are transcribed at late times after infection. Analysis of cDNAs of RNA transcripts of the terminal loop region of the viral DNA shows that both inverted and complementary forms of the terminal loop region are transcribe ... Full text Link to item Cite

Transcription of orthopoxvirus telomeres at late times during infection.

Journal Article Virology · March 1990 The telomeres of orthopoxvirus DNAs consists largely of short repeated sequences organized into at least two separate sets. Although the sequence composition of the orthopoxvirus telomeres is highly conserved, these regions do not appear to encode any prot ... Full text Link to item Cite

Vaccinia virus directs the synthesis of early mRNAs containing 5' poly(A) sequences.

Journal Article Proc Natl Acad Sci U S A · February 1990 Featured Publication mRNAs transcribed from late promoters of several poxvirus genes contain 5' poly(A) sequences that are not complementary to the viral DNA. In contrast, early mRNAs containing 5' poly(A) sequences have not previously been identified. Modifications to the seq ... Full text Link to item Cite

Fine structure mapping and phenotypic analysis of five temperature-sensitive mutations in the second largest subunit of vaccinia virus DNA-dependent RNA polymerase.

Journal Article Virology · January 1990 We have used plasmid clones spanning the region encoding the 132-kDa subunit of the cowpox virus RNA polymerase (CPV rpo 132) to marker rescue each of five vaccinia virus (VV) temperature sensitive (ts) mutants, ts 27, ts 29, ts 32, ts 47, and ts 62, which ... Full text Link to item Cite

Transcription of a poxvirus early gene is regulated both by a short promoter element and by a transcriptional termination signal controlling transcriptional interference.

Journal Article J Virol · November 1989 The promoter region of an early gene (38K gene) of cowpox virus has been characterized by deletion and linker scanning mutational analyses. Modified versions of this promoter region were placed into the genome of vaccinia virus, and their transcriptional e ... Full text Link to item Cite

Inhibition of an inflammatory response is mediated by a 38-kDa protein of cowpox virus.

Journal Article Virology · September 1989 The Brighton Red (BR) strain of cowpox virus induces a flat, bright red pock on the chorioallantoic membrane (CAM) of the 12-day-old chick embryo. In contrast, mutants with a deleted 38K gene (which is located 31 to 32 kb from the right-hand end of the vir ... Full text Link to item Cite

The second-largest subunit of the poxvirus RNA polymerase is similar to the corresponding subunits of procaryotic and eucaryotic RNA polymerases.

Journal Article J Virol · March 1989 We have characterized the poxvirus gene encoding the second-largest subunit of the viral DNA-dependent RNA polymerase. This gene, designated rpo132, is located in the HindIII A fragment of the DNA of the Brighton Red strain of cowpox virus. A similar gene ... Full text Link to item Cite

High-level synthesis of biologically active reovirus protein sigma 1 in a mammalian expression vector system.

Journal Article Virology · December 1988 The reovirus cell-attachment protein, which modulates tissue tropism and the nature of the antiviral immune response, is protein sigma 1. This protein is present in reovirus particles in the form of 12 tetramers anchored in the projections or spikes. It is ... Link to item Cite

A poxvirus-derived vector that directs high levels of expression of cloned genes in mammalian cells.

Journal Article Proc Natl Acad Sci U S A · December 1988 High levels of expression of cloned genes have been obtained in mammalian cells by using poxvirus-derived insertion/expression vectors. These vectors employ the cis-acting element (CAE I) that directs the transcription of one of the most strongly expressed ... Full text Link to item Cite

Virulence genes of poxviruses and reoviruses.

Journal Article Vaccine · April 1988 Identification of viral genes that specify virulence, however defined, is of critical importance for the design of viral vaccines. In particular, the targeted development not only of avirulent vaccine strains but also of viruses to be used as carriers for ... Full text Link to item Cite

Messenger RNAs of a strongly-expressed late gene of cowpox virus contain 5'-terminal poly(A) sequences.

Journal Article EMBO J · December 1, 1987 Featured Publication We have identified and characterized one of the most strongly-expressed genes of cowpox virus (CPV). This is the gene encoding the major protein component of the A-type inclusion bodies produced by this virus. This gene (designated the 160K gene) is transc ... Full text Link to item Cite

Tandemly repeated sequences are present at the ends of the DNA of raccoonpox virus.

Journal Article Virology · November 1987 The DNA of raccoonpox virus (RCN) has been characterized by restriction enzyme analysis. DNA hybridization studies showed that all HindIII fragments of the 215-kbp RCN DNA share some nucleotide sequence similarity with fragments of the DNA of cowpox virus ... Full text Link to item Cite

Hemorrhage in lesions caused by cowpox virus is induced by a viral protein that is related to plasma protein inhibitors of serine proteases.

Journal Article Proc Natl Acad Sci U S A · October 1986 Featured Publication Several recombinant cowpox viruses were constructed and used to identify a viral gene that controls the production of hemorrhage in lesions caused by the Brighton Red strain of cowpox virus (CPV-BR). This gene is located in the KpnD fragment of CPV-BR DNA, ... Full text Link to item Cite

Isolation of cowpox virus A-type inclusions and characterization of their major protein component.

Journal Article Virology · March 1986 A-type inclusions (ATI)2 are large well-defined structures that appear in the cytoplasm during the late stages of the multiplication cycles of many poxviruses. The ATIs produced by the CPRC1 strain of cowpox virus in strain 143 human osteosarcoma cells hav ... Full text Link to item Cite

Spontaneous deletions and duplications of sequences in the genome of cowpox virus.

Journal Article Proc Natl Acad Sci U S A · November 1984 Featured Publication Examination of the genomes of 10 white-pock variants of cowpox virus strain Brighton red (CPV-BR) revealed that 9 of them had lost 32 to 38 kilobase pairs (kbp) from their right-hand ends and that the deleted sequences had been replaced by inverted copies ... Full text Link to item Cite

Sequence of terminal regions of cowpox virus DNA: arrangement of repeated and unique sequence elements.

Journal Article Proc Natl Acad Sci U S A · December 1982 Featured Publication One terminal EcoRI fragment of the genome of cowpox virus (CPV) strain Brighton red has been cloned in plasmid pBR325, and the nucleotide sequence of the 2,725-base-pair Sal I fragment corresponding to that at the end of the viral genome has been determine ... Full text Link to item Cite