Mutation of chicken anemia virus VP2 differentially affects serine/threonine and tyrosine protein phosphatase activities

Royal Melbourne Hospital, Melbourne, Victoria, Australia
Journal of General Virology (Impact Factor: 3.18). 04/2005; 86(Pt 3):623-30. DOI: 10.1099/vir.0.80197-0
Source: PubMed


Novel dual-specificity protein phosphatases (DSPs), which catalyse the removal of phosphate from both phosphotyrosine and phosphoserine/phosphothreonine substrates, have recently been identified in two viruses within the family Circoviridae. Viral protein 2 (VP2) of chicken anemia virus (CAV) and ORF2 of TT virus have been shown to possess DSP activity in vitro. CAV VP2 is unusual in possessing two vicinal cysteines within the protein phosphatase signature motif. The first cysteine residue (C95) within the motif has been identified by mutagenesis as the essential catalytic cysteine. In this study, it was shown that virus mutated at this residue displayed a marked inhibition of growth, with titres reduced 10(4)-fold, and reduced cytopathogenic effect in cell culture, indicating that viral DSP activity may be significant during infection. As with virus mutated at the first cysteine residue, mutation of the second cysteine (C97) within the motif resulted in a marked reduction in viral growth and attenuation of cytopathogenicity in infected cell cultures. However, mutagenesis of this second cysteine only reduced phosphotyrosine phosphatase activity to 70 % of that of wild-type VP2, but increased phosphoserine/phosphothreonine phosphatase activity by as much as 700 %. The differential effect of the C97S mutation on VP2 activity does not appear to have parallels in other DSPs and suggests a unique role for the second cysteine in the function of these viral proteins, particularly in vivo.

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    • "VP2 has been shown to contain dual phosphatase activity and this activity is required for CAV replication [17,31]. However, in this context, very little is known about the role this protein plays in the regulation of viral DNA replication. "
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