Electron micrograph of vaccinia virus particles (courtesy of Dr. Sara Miller, Duke University)

Poxviruses are viruses that encode over 200 proteins and are unusually adept and sophisticated in targeting components of the immune system. Recently, the ways in which poxviruses modify cytokine-mediated responses to infection have been investigated. From this work, Dr. Pickup has shown that poxvirus affects immune responses 1) by preventing the synthesis of cytokines; 2) by encoding soluble secreted versions of receptors for cytokines; and 3) by interfering with cytokine signaling pathways. Currently, Dr. Pickup’s group is particularly interested in how poxviruses (in a species-specific way) positively or negatively affect the activation of NF-kappa B transcription factors, which are of critical importance in immune responses.

A major focus of the Pickup group is the development of improved vaccines against variola and related orthopoxviruses. As members of the Southeast Regional Center of Excellence in Emerging Infections and Biodefense (SERCEB), they are collaborating with investigators at the University of North Carolina at Chapel Hill (Dr. B. Johnston) and Emory University (Dr. D. Garber) to develop better virus-based vaccines against variola virus. In addition, they are working with Dr. Barbara Sherry at the College of Veterinary Medicine at North Carolina State University to investigate the effects of vaccinia virus-based vaccines upon cardiac cells and the heart. In these two vaccine projects, our goals are to develop potent vaccines that pose far fewer risks of complications than those currently available.

Knowledge of the fundamental mechanisms involved in poxviral interference with host processes should assist the development of therapies and vaccines for a variety of conditions associated with infectious diseases, inflammatory diseases, autoimmune diseases, cancers, and organ transplantation.