Work

Evolutionary clash between myxoma virus and rabbit PKR in Australia

Year: 2016

Type: editorial

Abstract: The success of a virus in defeating or evading cell-intrinsic immune responses contributes to its virulence, pathogenesis, and host range. A central tenet of virology holds that virus and host coevolve as each adapts to survive. Rarely, however, do we have the chance to observe this principal at play in the real world. The deliberate and repeated release of myxoma virus (MYXV) to control feral European rabbits introduced into Australia provides one such exceptional opportunity. Myxoma is a member of the poxvirus family, though unlike its more famous cousin variola, the agent of small pox, is unable to infect humans and is instead limited to infection of rabbits and hares. Following the release of a MYXV reference strain into the wild that exhibited 99.8% fatality rates in laboratory rabbits, attenuated strains were recovered from the field that had begun to outcompete the virulent parental strain. In addition, the resistance of rabbits to MYXV increased (1). The underlying molecular mechanism of both rabbit resistance and MYXV attenuation, however, remained elusive. Armed with the recently compiled genome sequence of 21 myxoma field isolates, a new study by Peng et al. in PNAS reveals that genetic alterations to the MYXV M156 protein correlate with both MYXV host specificity and changes in virulence observed in the field (2). Remarkably, more than 50% of MYXV field isolates produce an M156 variant that is no longer able to antagonize the rabbit double-stranded RNA (dsRNA)-activated protein kinase PKR, a critical component of IFN-stimulated defenses that controls protein synthesis. This not only provides the first mechanistic explanation for each of these facets of myxoma biology, but also elegantly illustrates the coevolution of host innate defense and viral virulence factors since the first release of MYXV in 1950. In response to virus infection, a key arm of … [↵][1]1To whom correspondence should be addressed. Email: ian.mohr{at}med.nyu.edu. [1]: #xref-corresp-1-1

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1602063113

Authors: Hannah M. Burgess, Ian Mohr

Institution: New York University

Language: English

Topic: Poxvirus research and outbreaks

Subfield: Virology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases