摘要: | Pseudorabies virus (PrV) belongs to the α-herpesvirinae of which human simplex virus (HSV) is the prototype virus.
One of the hallmarks of HSV infection is shutoff of protein synthesis that is mediated by various viral proteins including
vhs (virion host shutoff), which is encoded by the UL41 gene. However, the function of PrV vhs is poorly understood.
Due to the low sequence similarity (39.3%) between the HSV and PrV UL41 proteins, vhs might not share the
same biochemistry characteristics. The purpose of this study was to characterize the nuclease activity of the PrV vhs
protein with respect to substrate specificity, its requirements in terms of cofactors, and the protein regions, as well
as key amino acids, which contribute to vhs activity. Our results indicated that, similar to HSV vhs, PrV vhs is able to
degrade ssRNA and mRNA. However, PrV vhs also targeted rRNA for degradation, which is novel compared to the
HSV-1 vhs. Activity assays indicated that Mg2+ alone enhances RNA degradation mediated by PrV vhs, while K+ and
ATP are not sufficient to induce activity. Finally, we demonstrated that each of the four highly conserved functional
boxes of PrV vhs contributes to RNA degradation and that, in particular, residues 152, 169, 171, 172, 173 343, 345, 352
and 356, which are conserved among α-herpesviruses, are key amino acids needed for PrV vhs ribonuclease activity |