David James Pickup | Scholars@Duke

David James Pickup
Associate Professor Emeritus of Molecular Genetics and Microbiology

Viral inhibition of host immune defenses
Many viruses have evolved mechanisms to protect themselves from host immune defenses. Among this group are the orthopoxviruses, whose members include smallpox virus, one of the deadliest of human viruses, and cowpox virus, the virus that Edward Jenner used to begin the eradication of smallpox.

One of the especially interesting features of theses viruses is their ability to interfere with a wide range of innate and adaptive immune responses to infection. For example, we have found that cowpox virus inhibits inflammation by suppressing the actions of cytokines controlling inflammatory processes. Moreover, the virus does this in several ways: by preventing the synthesis of cytokines; by interfering with normal cytokine-receptor interactions; and by inhibiting cytokine-signaling pathways.

Our main research objectives are to identify mechanisms of virus-host interaction leading to the modification or alteration of host functions. Our working model is that such interactions are amongst the most important factors in viral pathogenesis. In addition, knowledge of these virus-host interactions should help in the development of new vaccines and therapies for a variety of conditions associated with infectious diseases, inflammatory diseases, autoimmune diseases, cancers, and organ transplantation.

Development of improved viral vaccines
Several excellent vaccine platforms exist, but among these vaccinia virus vaccines have unusual potential for targeting multiple different pathogens because of the extraordinary capacity of these vectors to encode multiple foreign proteins. Replication-defective vaccinia vectors are extremely safe. However, this safety comes at a cost. Because only a small amount of antigen can be produced during the single cycle of viral replication, vectors of this type typically require high doses and multiple boosts to induce protective immune responses. We are interested in finding ways to enhance the immunogenicity of these replication-defective vaccine viruses without compromising on safety.

Current Appointments & Affiliations

Associate Professor Emeritus of Molecular Genetics and Microbiology, Molecular Genetics and Microbiology, Basic Science Departments 2018
Member of the Duke Human Vaccine Institute, Duke Human Vaccine Institute, Institutes and Centers 2006

Contact Information

421 Jones Bldg, Durham, NC 27710
Duke Box 3020, Durham, NC 27710
david.pickup@dm.duke.edu (919) 539-8065

Background
Education, Training, & Certifications
- Ph.D., National Institute for Medical Research, London (United Kingdom) 1979
Duke Appointment History
- Member of the Duke Cancer Institute, Duke Cancer Institute, Institutes and Centers 1979 - 2018
- Associate Professor of Virology in the Department of Molecular Genetics and Microbiology, Molecular Genetics and Microbiology, Basic Science Departments 2002 - 2017
- Associate Professor of Virology in the Department of Microbiology, Molecular Genetics and Microbiology, Basic Science Departments 1995 - 2002
- Assistant Professor of Virology in the Department of Microbiology, Molecular Genetics and Microbiology, Basic Science Departments 1985 - 1994
Research
Selected Grants
- Genetics Training Grant awarded by National Institutes of Health 1979 - 2020
- Novel Recombinant Streptococcus mitis as an oral vaccine against HIV/AIDS awarded by Forsyth Institute 2017 - 2018
- Mucosal vaccination to protect against HIV-1 infection at mucosal sites awarded by National Institutes of Health 2012 - 2017
- Large Scale Antibody and TCell Epitope Discovery awarded by National Institutes of Health 2004 - 2011
- Viral Inhibition of Host Defenses awarded by National Institutes of Health 1995 - 2002
- Viral Inhibition Of Host Defenses awarded by National Institutes of Health 1992 - 1999
- Cancer Center Core Support Grant awarded by National Institutes of Health 1976 - 1998
- Comprehensive Cancer Center Core Support Grant awarded by National Institutes of Health 1976 - 1998
- Comprehensive Cancer Center Core Support Grant awarded by National Institutes of Health 1976 - 1998
- The Inhibition Of Inflammatory Processes awarded by National Institutes of Health 1993 - 1995
- The Inhibition Of Inflammatory Processes awarded by National Institutes of Health 1992 - 1995
- Structure And Function Of Poxvirus Genes awarded by National Institutes of Health 1993 - 1995
- The Structure And Function Of Poxvirus Genes awarded by National Institutes of Health 1986 - 1989
Publications & Artistic Works
Selected Publications
- Academic Articles
  - Jones, Dorothy I., Justin J. Pollara, Brandi T. Johnson-Weaver, Celia C. LaBranche, David C. Montefiori, David J. Pickup, Sallie R. Permar, et al. “Optimized Mucosal Modified Vaccinia Virus Ankara Prime/Soluble gp120 Boost HIV Vaccination Regimen Induces Antibody Responses Similar to Those of an Intramuscular Regimen.” J Virol 93, no. 14 (July 15, 2019). https://doi.org/10.1128/JVI.00475-19.
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  - Eudailey, Joshua A., Maria L. Dennis, Morgan E. Parker, Bonnie L. Phillips, Tori N. Huffman, Camden P. Bay, Michael G. Hudgens, et al. “Maternal HIV-1 Env Vaccination for Systemic and Breast Milk Immunity To Prevent Oral SHIV Acquisition in Infant Macaques.” Msphere 3, no. 1 (January 2018). https://doi.org/10.1128/mSphere.00505-17.
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  - Jones, Dorothy I., Charles E. McGee, Christopher J. Sample, Gregory D. Sempowski, David J. Pickup, and Herman F. Staats. “Modified Vaccinia Ankara Virus Vaccination Provides Long-Term Protection against Nasal Rabbitpox Virus Challenge.” Clin Vaccine Immunol 23, no. 7 (July 2016): 648–51. https://doi.org/10.1128/CVI.00216-16.
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  - Nelson, Cody S., Justin Pollara, Erika L. Kunz, Thomas L. Jeffries, Ryan Duffy, Charles Beck, Lisa Stamper, et al. “Combined HIV-1 Envelope Systemic and Mucosal Immunization of Lactating Rhesus Monkeys Induces a Robust Immunoglobulin A Isotype B Cell Response in Breast Milk.” J Virol 90, no. 10 (May 15, 2016): 4951–65. https://doi.org/10.1128/JVI.00335-16.
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  - Pickup, David J. “Extracellular Virions: The Advance Guard of Poxvirus Infections.” Plos Pathog 11, no. 7 (July 2015): e1004904. https://doi.org/10.1371/journal.ppat.1004904.
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  - Alzhanova, Dina, Erika Hammarlund, Jason Reed, Erin Meermeier, Stephanie Rawlings, Caroline A. Ray, David M. Edwards, et al. “T cell inactivation by poxviral B22 family proteins increases viral virulence.” Plos Pathog 10, no. 5 (May 2014): e1004123. https://doi.org/10.1371/journal.ppat.1004123.
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  - Fouda, Genevieve G. A., Joshua D. Amos, Andrew B. Wilks, Justin Pollara, Caroline A. Ray, Anjali Chand, Erika L. Kunz, et al. “Mucosal immunization of lactating female rhesus monkeys with a transmitted/founder HIV-1 envelope induces strong Env-specific IgA antibody responses in breast milk.” J Virol 87, no. 12 (June 2013): 6986–99. https://doi.org/10.1128/JVI.00528-13.
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  - Pollara, Justin J., April H. Spesock, David J. Pickup, Scott M. Laster, and Ian T. D. Petty. “Production of prostaglandin E₂ in response to infection with modified vaccinia Ankara virus.” Virology 428, no. 2 (July 5, 2012): 146–55. https://doi.org/10.1016/j.virol.2012.03.019.
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  - Spesock, April H., Brice E. Barefoot, Caroline A. Ray, Daniel J. Kenan, Michael D. Gunn, Elizabeth A. Ramsburg, and David J. Pickup. “Cowpox virus induces interleukin-10 both in vitro and in vivo.” Virology 417, no. 1 (August 15, 2011): 87–97. https://doi.org/10.1016/j.virol.2011.05.010.
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  - Hansen, Spencer J., John Rushton, Alexander Dekonenko, Hitendra S. Chand, Gwyneth K. Olson, Julie A. Hutt, David Pickup, C Rick Lyons, and Mary F. Lipscomb. “Cowpox virus inhibits human dendritic cell immune function by nonlethal, nonproductive infection.” Virology 412, no. 2 (April 10, 2011): 411–25. https://doi.org/10.1016/j.virol.2011.01.024.
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  - Pickup, David J. “Cell biology. Propelling progeny.” Science 327, no. 5967 (February 12, 2010): 787–88. https://doi.org/10.1126/science.1187160.
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  - Byun, Minji, Marieke C. Verweij, David J. Pickup, Emmanuel J. H. J. Wiertz, Ted H. Hansen, and Wayne M. Yokoyama. “Two mechanistically distinct immune evasion proteins of cowpox virus combine to avoid antiviral CD8 T cells.” Cell Host Microbe 6, no. 5 (November 19, 2009): 422–32. https://doi.org/10.1016/j.chom.2009.09.012.
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  - Lynch, Heather E., Caroline A. Ray, Katrina L. Oie, Justin J. Pollara, Ian T. D. Petty, Anthony J. Sadler, Bryan R. G. Williams, and David J. Pickup. “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.” Virology 391, no. 2 (September 1, 2009): 177–86. https://doi.org/10.1016/j.virol.2009.06.012.
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  - Thornburg, Natalie J., Caroline A. Ray, Martha L. Collier, Hua-Xin Liao, David J. Pickup, and Robert E. Johnston. “Vaccination with Venezuelan equine encephalitis replicons encoding cowpox virus structural proteins protects mice from intranasal cowpox virus challenge.” Virology 362, no. 2 (June 5, 2007): 441–52. https://doi.org/10.1016/j.virol.2007.01.001.
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  - Pickup, David J. “Understanding orthopoxvirus interference with host immune responses to inform novel vaccine design.” Expert Rev Vaccines 6, no. 1 (February 2007): 87–95. https://doi.org/10.1586/14760584.6.1.87.
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  - D’Costa, Susan M., James B. Antczak, David J. Pickup, and Richard C. Condit. “Post-transcription cleavage generates the 3' end of F17R transcripts in vaccinia virus.” Virology 319, no. 1 (February 5, 2004): 1–11. https://doi.org/10.1016/j.virol.2003.09.041.
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  - McKelvey, Terry A., Stanley C. Andrews, Sara E. Miller, Caroline A. Ray, and David J. Pickup. “Identification of the orthopoxvirus p4c gene, which encodes a structural protein that directs intracellular mature virus particles into A-type inclusions.” J Virol 76, no. 22 (November 2002): 11216–25. https://doi.org/10.1128/jvi.76.22.11216-11225.2002.
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  - Panus, Joanne Fanelli, Craig A. Smith, Caroline A. Ray, Terri Davis Smith, Dhavalkumar D. Patel, and David J. Pickup. “Cowpox virus encodes a fifth member of the tumor necrosis factor receptor family: a soluble, secreted CD30 homologue.” Proc Natl Acad Sci U S A 99, no. 12 (June 11, 2002): 8348–53. https://doi.org/10.1073/pnas.122238599.
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  - Oie, K. L., and D. J. Pickup. “Cowpox virus and other members of the orthopoxvirus genus interfere with the regulation of NF-kappaB activation.” Virology 288, no. 1 (September 15, 2001): 175–87. https://doi.org/10.1006/viro.2001.1090.
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  - Howard, S. T., C. A. Ray, D. D. Patel, J. B. Antczak, and D. J. Pickup. “A 43-nucleotide RNA cis-acting element governs the site-specific formation of the 3' end of a poxvirus late mRNA.” Virology 255, no. 1 (March 1, 1999): 190–204. https://doi.org/10.1006/viro.1998.9547.
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  - Loparev, V. N., J. M. Parsons, J. C. Knight, J. F. Panus, C. A. Ray, R. M. Buller, D. J. Pickup, and J. J. Esposito. “A third distinct tumor necrosis factor receptor of orthopoxviruses.” Proc Natl Acad Sci U S A 95, no. 7 (March 31, 1998): 3786–91. https://doi.org/10.1073/pnas.95.7.3786.
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  - Smith, C. A., T. D. Smith, P. J. Smolak, D. Friend, H. Hagen, M. Gerhart, L. Park, et al. “Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits beta chemokine activity yet lacks sequence homology to known chemokine receptors.” Virology 236, no. 2 (September 29, 1997): 316–27. https://doi.org/10.1006/viro.1997.8730.
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  - Smith, C. A., F. Q. Hu, T. D. Smith, C. L. Richards, P. Smolak, R. G. Goodwin, and D. J. Pickup. “Cowpox virus genome encodes a second soluble homologue of cellular TNF receptors, distinct from CrmB, that binds TNF but not LT alpha.” Virology 223, no. 1 (September 1, 1996): 132–47. https://doi.org/10.1006/viro.1996.0462.
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  - Quan, L. T., M. Tewari, K. O’Rourke, V. Dixit, S. J. Snipas, G. G. Poirier, C. Ray, D. J. Pickup, and G. S. Salvesen. “Proteolytic activation of the cell death protease Yama/CPP32 by granzyme B.” Proc Natl Acad Sci U S A 93, no. 5 (March 5, 1996): 1972–76. https://doi.org/10.1073/pnas.93.5.1972.
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  - Ray, C. A., and D. J. Pickup. “The mode of death of pig kidney cells infected with cowpox virus is governed by the expression of the crmA gene.” Virology 217, no. 1 (March 1, 1996): 384–91. https://doi.org/10.1006/viro.1996.0128.
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  - Quan, L. T., A. Caputo, R. C. Bleackley, D. J. Pickup, and G. S. Salvesen. “Granzyme B is inhibited by the cowpox virus serpin cytokine response modifier A.” J Biol Chem 270, no. 18 (May 5, 1995): 10377–79. https://doi.org/10.1074/jbc.270.18.10377.
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  - Howard, A. D., O. C. Palyha, P. R. Griffin, E. P. Peterson, A. B. Lenny, G. J. Ding, D. J. Pickup, N. A. Thornberry, J. A. Schmidt, and M. J. Tocci. “Human IL-1 beta processing and secretion in recombinant baculovirus-infected Sf9 cells is blocked by the cowpox virus serpin crmA.” J Immunol 154, no. 5 (March 1, 1995): 2321–32.
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  - Hu, F. Q., C. A. Smith, and D. J. Pickup. “Cowpox virus contains two copies of an early gene encoding a soluble secreted form of the type II TNF receptor.” Virology 204, no. 1 (October 1994): 343–56. https://doi.org/10.1006/viro.1994.1539.
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  - Komiyama, T., C. A. Ray, D. J. Pickup, A. D. Howard, N. A. Thornberry, E. P. Peterson, and G. Salvesen. “Inhibition of interleukin-1 beta converting enzyme by the cowpox virus serpin CrmA. An example of cross-class inhibition.” J Biol Chem 269, no. 30 (July 29, 1994): 19331–37.
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  - Pickup, D. J. “Poxviral modifiers of cytokine responses to infection.” Infect Agents Dis 3, no. 2–3 (April 1994): 116–27.
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  - Antczak, J. B., D. D. Patel, C. A. Ray, B. S. Ink, and D. J. Pickup. “Site-specific RNA cleavage generates the 3' end of a poxvirus late mRNA.” Proc Natl Acad Sci U S A 89, no. 24 (December 15, 1992): 12033–37. https://doi.org/10.1073/pnas.89.24.12033.
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  - Spriggs, M. K., D. E. Hruby, C. R. Maliszewski, D. J. Pickup, J. E. Sims, R. M. Buller, and J. VanSlyke. “Vaccinia and cowpox viruses encode a novel secreted interleukin-1-binding protein.” Cell 71, no. 1 (October 2, 1992): 145–52. https://doi.org/10.1016/0092-8674(92)90273-f.
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  - Gierman, T. M., R. M. Frederickson, N. Sonenberg, and D. J. Pickup. “The eukaryotic translation initiation factor 4E is not modified during the course of vaccinia virus replication.” Virology 188, no. 2 (June 1992): 934–37. https://doi.org/10.1016/0042-6822(92)90557-6.
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  - Ray, C. A., R. A. Black, S. R. Kronheim, T. A. Greenstreet, P. R. Sleath, G. S. Salvesen, and D. J. Pickup. “Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme.” Cell 69, no. 4 (May 15, 1992): 597–604. https://doi.org/10.1016/0092-8674(92)90223-y.
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  - Hu, F. Q., and D. J. Pickup. “Transcription of the terminal loop region of vaccinia virus DNA is initiated from the telomere sequences directing DNA resolution.” Virology 181, no. 2 (April 1991): 716–20. https://doi.org/10.1016/0042-6822(91)90905-q.
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  - Parsons, B. L., and D. J. Pickup. “Transcription of orthopoxvirus telomeres at late times during infection.” Virology 175, no. 1 (March 1990): 69–80. https://doi.org/10.1016/0042-6822(90)90187-v.
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  - Ink, B. S., and D. J. Pickup. “Vaccinia virus directs the synthesis of early mRNAs containing 5' poly(A) sequences.” Proc Natl Acad Sci U S A 87, no. 4 (February 1990): 1536–40. https://doi.org/10.1073/pnas.87.4.1536.
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  - Hooda-Dhingra, U., D. D. Patel, D. J. Pickup, and R. C. Condit. “Fine structure mapping and phenotypic analysis of five temperature-sensitive mutations in the second largest subunit of vaccinia virus DNA-dependent RNA polymerase.” Virology 174, no. 1 (January 1990): 60–69. https://doi.org/10.1016/0042-6822(90)90054-u.
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  - Ink, B. S., and D. J. Pickup. “Transcription of a poxvirus early gene is regulated both by a short promoter element and by a transcriptional termination signal controlling transcriptional interference.” J Virol 63, no. 11 (November 1989): 4632–44. https://doi.org/10.1128/JVI.63.11.4632-4644.1989.
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  - Palumbo, G. J., D. J. Pickup, T. N. Fredrickson, L. J. McIntyre, and R. M. Buller. “Inhibition of an inflammatory response is mediated by a 38-kDa protein of cowpox virus.” Virology 172, no. 1 (September 1989): 262–73. https://doi.org/10.1016/0042-6822(89)90128-1.
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  - Patel, D. D., and D. J. Pickup. “The second-largest subunit of the poxvirus RNA polymerase is similar to the corresponding subunits of procaryotic and eucaryotic RNA polymerases.” J Virol 63, no. 3 (March 1989): 1076–86. https://doi.org/10.1128/JVI.63.3.1076-1086.1989.
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  - Banerjea, A. C., K. A. Brechling, C. A. Ray, H. Erikson, D. J. Pickup, and W. K. Joklik. “High-level synthesis of biologically active reovirus protein sigma 1 in a mammalian expression vector system.” Virology 167, no. 2 (December 1988): 601–12.
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  - Patel, D. D., C. A. Ray, R. P. Drucker, and D. J. Pickup. “A poxvirus-derived vector that directs high levels of expression of cloned genes in mammalian cells.” Proc Natl Acad Sci U S A 85, no. 24 (December 1988): 9431–35. https://doi.org/10.1073/pnas.85.24.9431.
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  - Joklik, W. K., D. J. Pickup, D. D. Patel, and M. D. Moody. “Virulence genes of poxviruses and reoviruses.” Vaccine 6, no. 2 (April 1988): 123–28. https://doi.org/10.1016/s0264-410x(88)80013-6.
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  - Patel, D. D., and D. J. Pickup. “Messenger RNAs of a strongly-expressed late gene of cowpox virus contain 5'-terminal poly(A) sequences.” Embo J 6, no. 12 (December 1, 1987): 3787–94.
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  - Parsons, B. L., and D. J. Pickup. “Tandemly repeated sequences are present at the ends of the DNA of raccoonpox virus.” Virology 161, no. 1 (November 1987): 45–53. https://doi.org/10.1016/0042-6822(87)90169-3.
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  - Pickup, D. J., B. S. Ink, W. Hu, C. A. Ray, and W. K. Joklik. “Hemorrhage in lesions caused by cowpox virus is induced by a viral protein that is related to plasma protein inhibitors of serine proteases.” Proc Natl Acad Sci U S A 83, no. 20 (October 1986): 7698–7702. https://doi.org/10.1073/pnas.83.20.7698.
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  - Patel, D. D., D. J. Pickup, and W. K. Joklik. “Isolation of cowpox virus A-type inclusions and characterization of their major protein component.” Virology 149, no. 2 (March 1986): 174–89. https://doi.org/10.1016/0042-6822(86)90119-4.
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  - Pickup, D. J., B. S. Ink, B. L. Parsons, W. Hu, and W. K. Joklik. “Spontaneous deletions and duplications of sequences in the genome of cowpox virus.” Proc Natl Acad Sci U S A 81, no. 21 (November 1984): 6817–21. https://doi.org/10.1073/pnas.81.21.6817.
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  - Pickup, D. J., D. Bastia, and W. K. Joklik. “Cloning of the terminal loop of vaccinia virus DNA.” Virology 124, no. 1 (January 15, 1983): 215–17. https://doi.org/10.1016/0042-6822(83)90309-4.
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  - Pickup, D. J., D. Bastia, H. O. Stone, and W. K. Joklik. “Sequence of terminal regions of cowpox virus DNA: arrangement of repeated and unique sequence elements.” Proc Natl Acad Sci U S A 79, no. 23 (December 1982): 7112–16. https://doi.org/10.1073/pnas.79.23.7112.
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  - Antczak, J. B., R. Chmelo, D. J. Pickup, and W. K. Joklik. “Sequence at both termini of the 10 genes of reovirus serotype 3 (strain Dearing).” Virology 121, no. 2 (September 1982): 307–19. https://doi.org/10.1016/0042-6822(82)90170-2.
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- Book Sections
  - Komiyama, T., T., L. Quan, S. Snipas, C. A. Ray, D. J. Pickup, and G. Salvesen. “In vitro expression of serpins.” In Techniques in Protein Chemistry V, edited by J. W. Crabb, 305–12. New York: Academic Press, 1994.
  - Pickup, D. J. “Molecular cloning of the IL-1β processing enzyme.” In Pathophysiology and Pharmacology of Cytokines, edited by P. Ghezzi, and A. Mantovani, 3–8. Augusta, Georgia, USA: Biomedical Press, 1992.
- Other Articles
  - Pickup, David J. “Poxviruses.” John Wiley & Sons, Ltd, n.d. https://doi.org/10.1002/9780470015902.a0001083.pub3.
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- Book Reviews
  - Pickup, D. J. “Book review: 'The orthopoxviruses' (F. Fenner, R. Wittek, and K.R. Dumbell).” Cell, January 1, 1989.
- Conference Papers
  - Komiyama, T., L. Quan, S. Snipas, C. A. Ray, D. J. Pickup, and G. Salvesen. “In Vitro Expression of Serpins,” 5:305–12, 1994. https://doi.org/10.1016/B978-0-12-194710-1.50039-4.
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  - PICKUP, D. J., F. Q. HU, R. G. GOODWIN, T. DAVIS, and C. SMITH. “SOLUBLE TUMOR-NECROSIS-FACTOR RECEPTORS OF 2 TYPES ARE ENCODED BY COWPOX VIRUS.” In Journal of Cellular Biochemistry, 81–81. WILEY-LISS, 1993.
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Teaching & Mentoring
Recent Courses

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Education, Training, & Certifications

Duke Appointment History

Selected Grants

Selected Publications

Academic Articles

Book Sections

Other Articles

Book Reviews

Conference Papers

Recent Courses