David James Pickup, PhD


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Associate Professor of Virology in the Department of Molecular Genetics and Microbiology
Molecular Genetics and Microbiology
421 Jones Bldg
Durham, NC 27710
Office Telephone:
(919) 684-2480
  • PhD, National Institute for Medical Research, London, 1979
Research Interests:
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.

Representative Publications:
  • Byun, M; Verweij, MC; Pickup, DJ; Wiertz, EJ; Hansen, TH; Yokoyama, WM. Two mechanistically distinct immune evasion proteins of cowpox virus combine to avoid antiviral CD8 T cells. Cell Host and Microbe. 2009;6:422-432.  Abstract
  • Lynch, HE; Ray, CA; Oie, KL; Pollara, JJ; Petty, IT; Sadler, AJ; Williams, BR; Pickup, DJ. 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. 2009;391:177-186.  Abstract
  • Pickup, DJ. Understanding orthopoxvirus interference with host immune responses to inform novel vaccine design. Expert Review of Vaccines. 2007;6:87-95.  Abstract
  • Thornburg, NJ; Ray, CA; Collier, ML; Liao, HX; Pickup, DJ; Johnston, RE. Vaccination with Venezuelan equine encephalitis replicons encoding cowpox virus structural proteins protects mice from intranasal cowpox virus challenge. Virology. 2007;362:441-452.  Abstract
  • D'Costa, SM; Antczak, JB; Pickup, DJ; Condit, RC. Post-transcription cleavage generates the 3' end of F17R transcripts in vaccinia virus. Virology. 2004;319:1-11.  Abstract
  • McKelvey, TA; Andrews, SC; Miller, SE; Ray, CA; Pickup, DJ. Identification of the orthopoxvirus p4c gene, which encodes a structural protein that directs intracellular mature virus particles into A-type inclusions. Journal of virology. 2002;76:11216-11225.  Abstract
  • Panus, JF; Smith, CA; Ray, CA; Smith, TD; Patel, DD; Pickup, DJ. Cowpox virus encodes a fifth member of the tumor necrosis factor receptor family: a soluble, secreted CD30 homologue. Proceedings of the National Academy of Sciences of USA. 2002;99:8348-8353.  Abstract
  • Oie, KL; Pickup, DJ. Cowpox virus and other members of the orthopoxvirus genus interfere with the regulation of NF-kappaB activation. Virology. 2001;288:175-187.  Abstract
  • Howard, ST; Ray, CA; Patel, DD; Antczak, JB; Pickup, DJ. A 43-nucleotide RNA cis-acting element governs the site-specific formation of the 3' end of a poxvirus late mRNA. Virology. 1999;255:190-204.  Abstract
  • Loparev, VN; Parsons, JM; Knight, JC; Panus, JF; Ray, CA; Buller, RM; Pickup, DJ; Esposito, JJ. A third distinct tumor necrosis factor receptor of orthopoxviruses. Proceedings of the National Academy of Sciences of USA. 1998;95:3786-3791.  Abstract
  • Smith, CA; Smith, TD; Smolak, PJ; Friend, D; Hagen, H; Gerhart, M; Park, L; Pickup, DJ; Torrance, D; Mohler, K; Schooley, K; Goodwin, RG. Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits beta chemokine activity yet lacks sequence homology to known chemokine receptors. Virology. 1997;236:316-327.  Abstract
  • Quan, LT; Tewari, M; O'Rourke, K; Dixit, V; Snipas, SJ; Poirier, GG; Ray, C; Pickup, DJ; Salvesen, GS. Proteolytic activation of the cell death protease Yama/CPP32 by granzyme B. Proceedings of the National Academy of Sciences of USA. 1996;93:1972-1976.  Abstract
  • Smith, CA; Hu, FQ; Smith, TD; Richards, CL; Smolak, P; Goodwin, RG; Pickup, DJ. Cowpox virus genome encodes a second soluble homologue of cellular TNF receptors, distinct from CrmB, that binds TNF but not LT alpha. Virology. 1996;223:132-147.  Abstract
  • Hu, FQ; Smith, CA; Pickup, DJ. Cowpox virus contains two copies of an early gene encoding a soluble secreted form of the type II TNF receptor. Virology. 1994;204:343-356.  Abstract
  • Antczak, JB; Patel, DD; Ray, CA; Ink, BS; Pickup, DJ. Site-specific RNA cleavage generates the 3' end of a poxvirus late mRNA. Proceedings of the National Academy of Sciences of USA. 1992;89:12033-12037.  Abstract
  • Ray, CA; Black, RA; Kronheim, SR; Greenstreet, TA; Sleath, PR; Salvesen, GS; Pickup, DJ. Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme. Cell. 1992;69:597-604.  Abstract
  • Spriggs, MK; Hruby, DE; Maliszewski, CR; Pickup, DJ; Sims, JE; Buller, RM; VanSlyke, J. Vaccinia and cowpox viruses encode a novel secreted interleukin-1-binding protein. Cell. 1992;71:145-152.  Abstract
  • Ink, BS; Pickup, DJ. Vaccinia virus directs the synthesis of early mRNAs containing 5' poly(A) sequences. Proceedings of the National Academy of Sciences of USA. 1990;87:1536-1540.  Abstract
  • Patel, DD; Pickup, DJ. Messenger RNAs of a strongly-expressed late gene of cowpox virus contain 5'-terminal poly(A) sequences. EMBO Journal. 1987;6:3787-3794.  Abstract
  • Pickup, DJ; Ink, BS; Hu, W; Ray, CA; Joklik, WK. Hemorrhage in lesions caused by cowpox virus is induced by a viral protein that is related to plasma protein inhibitors of serine proteases. Proceedings of the National Academy of Sciences of USA. 1986;83:7698-7702.  Abstract
  • Pickup, DJ; Ink, BS; Parsons, BL; Hu, W; Joklik, WK. Spontaneous deletions and duplications of sequences in the genome of cowpox virus. Proceedings of the National Academy of Sciences of USA. 1984;81:6817-6821.  Abstract
  • Pickup, DJ; Bastia, D; Stone, HO; Joklik, WK. Sequence of terminal regions of cowpox virus DNA: arrangement of repeated and unique sequence elements. Proceedings of the National Academy of Sciences of USA. 1982;79:7112-7116.  Abstract