35 Poxvirus

Abstract

Poxviruses are large, enveloped, DNA viruses that infect vertebrate or invertebrate species, replicate entirely in the cytoplasm, and encode proteins with roles in gene expression, DNA synthesis, virion assembly, and host evasion (Moss 2001). Two poxviruses are human-specific: Variola virus and Molluscum contagiosum virus. The former causes smallpox, a severe disease with high mortality that was eradicated more than two decades ago; the latter is distributed worldwide and produces discrete benign skin lesions in infants but more extensive disease in immunocompromised individuals. In addition, other poxviruses that infect nonhuman species can be transmitted to humans (Appendix, Table VII). Vaccinia virus (VACV), the vaccine used to prevent smallpox, is the prototype of the family, and cited experiments relate to this virus unless stated otherwise.

The VACV genome, together with viral enzymes and factors required for transcription of the early subset of genes, is packaged in the core of infectious virus particles (Moss 2001). Consequently, viral early RNA synthesis occurs soon after entry of the core into the cytoplasm, without a requirement for de novo protein synthesis. The necessity to import the viral transcription system explains why poxvirus genomic DNA is not infectious and why a helper poxvirus is required to recover infectivity from a bacterial artificial chromosome containing a complete VACV genome (Domi and Moss 2002). The DNA replication proteins, in contrast to those involved in early transcription, are not packaged in virions but are translated from viral early mRNAs. The latter also encode proteins with roles in transcription of intermediate-stage...