One for the virus geeks

VPg

Success of a virus infection requires that each infected cell delivers a sufficient number of infectious particles to allow new rounds of infection. In picornaviruses, virus replication is initiated by the viral polymerase and a viral-coded protein, termed VPg, that primes RNA synthesis. Foot-and-mouth disease virus (FMDV) is exceptional among picornaviruses in that its genome encodes three copies of VPg. Why FMDV encodes three VPgs is unknown.

Researchers constructed four mutant FMDVs that encode only one VPg: either VPg1, VPg3, or two chimeric versions containing part of VPg1 and VPg3. All mutants, except that encoding only VPg1, were replication-competent. Unexpectedly, despite being replication-competent, the mutants did not form plaques on BHK-21 cell monolayers. The one-VPg mutant FMDVs released lower amounts of encapsidated viral RNA to the extracellular environment than wild type FMDV, suggesting that deficient plaque formation was associated with insufficient release of infectious progeny. Mutant FMDVs subjected to serial passages in BHK-21 cells regained plaque-forming capacity without modification of the number of copies of VPg. Substitutions in non-structural proteins 2C, 3A and VPg were associated with restoration of plaque formation. Specifically, replacement R55W in protein 2C was repeatedly found in several mutant viruses that had regained competence in plaque development. The results link the VPg copies in the FMDV genome with the cytopathology capacity of the virus, and have unveiled yet another function of 2C: modulation of picornavirus cell-to-cell transmission. these data highlight the role of non–structural proteins in the adaptability to changing environments during picornavirus infections, with clear implications for viral pathogenesis.

Deletion Mutants of VPg Reveal New Cytopathology Determinants in a Picornavirus. 2010 PLoS ONE 5(5): e10735. doi:10.1371/journal.pone.0010735

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