Vaccinia virus and other poxviruses express a wide variety of proteins which are non-essential for virus replication in culture but help the virus to evade the host response to infection. Examples include proteins which oppose apoptosis, synthesise steroids, capture chemokines, counteract complement, interfere with interferon and intercept interleukins. This review provides an overview of such proteins, with an emphasis on work from our laboratory, and illustrates how the study of these proteins can increase our understanding of virus pathogenesis, the function of the immune system and how to make safer and more immunogenic poxvirus-based vaccines.

The vaccinia virus (VV) strain

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Poxviruses encode soluble cytokine receptors to interfere with host immune functions. Cells infected with vaccinia virus (VV) strains USSR, Lister, and Evans express soluble and cell surface tumor necrosis factor receptors (vTNFRs). We have characterized vTNFR activity in VV USSR and identified an open reading frame that encodes both soluble and cell surface activity, hereafter referred to as VV cytokine response modifier E (VV CrmE). Expression and characterization from recombinant VV and baculovirus showed VV CrmE to be an 18-kDa protein that bound human, mouse, and rat TNF-alpha, but not human LT alpha. VV CrmE inhibited the cytotoxic and apoptotic activities of human, but not mouse or rat, TNF in vitro. Nonetheless, in a murine intranasal model, USSR recombinants lacking CrmE were attenuated, demonstrating a role in vivo. Furthermore, expression of VV or cowpox virus vTNFRs from VV strain WR (which itself does not express a vTNFR) was shown to enhance virulence in the murine model.

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