Poxviruses and the evolution of host range and virulence

Abstract

Poxviruses as a group can infect a large number of animals. However, at the level of individual viruses, even closely related poxviruses display highly diverse host ranges and virulence. For example, variola virus, the causative agent of smallpox, is human-specific and highly virulent only to humans, whereas related cowpox viruses naturally infect a broad spectrum of animals and only cause relatively mild disease in humans. The successful replication of poxviruses depends on their effective manipulation of the host antiviral responses, at the cellular-, tissue- and species-specific levels, which constitutes a molecular basis for differences in poxvirus host range and virulence. A number of poxvirus genes have been identified that possess host range function in experimental settings, and many of these host range genes target specific antiviral host pathways. Herein, we review the biology of poxviruses with a focus on host range, zoonotic infections, virulence, genomics and host range genes as well as the current knowledge about the function of poxvirus host range factors and how their interaction with the host innate immune system contributes to poxvirus host range and virulence. We further discuss the evolution of host range and virulence in poxviruses as well as host switches and potential poxvirus threats for human and animal health.

Triad of human cellular proteins, IRF2, FAM111A, and RFC3, restrict replication of orthopoxvirus SPI-1 host-range mutants

“…The numerous viral genes devoted to host interactions provide a living record of the natural selection that has occurred over millennia. Indeed, such genes constitute approximately half of the large DNA genomes of poxviruses (2,3). In general, the defense genes can be recognized by their location near the ends of the genome and their variability compared with the ∼100 genes highly conserved in all vertebrate poxviruses that are needed for replication and dissemination (4).…”

Orthopoxvirus infection among wildlife in Zambia

“…The serological evidence of OPXV exposure indicates that several species of common African wild animals are susceptible to OPXV infection. MPXV, CPXV and VACV are also known to naturally infect very broad ranges of mammalian species (Essbauer et al, 2010;Haller et al, 2014) and CPXV infection of shrews has been reported (Laakkonen et al, 2006;Tryland et al, 1998).…”

Innate immune activation of NFκB and its antagonism by poxviruses

“…This 'host range' can be experimentally correlated with the presence of defined 'host range genes' which are commonly immunomodulators that block divergent host specific anti-viral responses [4]. These genes are under strong evolutionary selection and vary dramatically even between similar species within a genus [5].…”