Poxvirus immunomodulatory strategies: Current perspectives

Successful transmission by viruses in the face of vigorous innate and acquired host immunity requires the ability to evade, obstruct, or subvert critical elements that mediate host antiviral responses. To that end, viruses with larger genomes, such as poxviruses, encode multiple classes of immunomodulatory proteins that have evolved specifically to inhibit such diverse processes as apoptosis, the production of interferons, chemokines, and inflammatory cytokines, and the activity of cytotoxic T lymphocytes (CTLs), natural killer (NK) cells, complement, and antibodies. Often, the evolutionary origins of these virus-encoded immunomodulatory proteins are difficult to trace. The obvious sequence similarity between some immunomodulatory poxvirus genes and the cDNA versions of related cellular counterparts suggests that they were once captured by ancestral retrotranscription and/or recombination events and then reassorted into individual virus isolates during coevolution with vertebrate hosts. However, other poxviral immunomodulators have no known cellular counterpart or have putative functions that cannot be predicted based on similarity to known cellular proteins. The origins of these orphan regulators may be obscure, but their potential for immune subversion can be profound.