The Virion Host Shutoff Protein of Herpes Simplex Virus Inhibits Reporter Gene Expression in the Absence of Other Viral Gene Products

The virion host shutoff (vhs) function of herpes simplex virus induces degradation of host mRNAs at early times and rapid turnover of vital mRNAs throughout infection. Previous studies have shown that disruption of the UL41 gene abrogates vhs activity, but have not determined whether the UL41 polypeptide is the direct inducer of mRNA degradation or whether it is the only virion component required for this activity. In this paper we report that transfaction of cells with UL41 inhibits expression of a cotransfected CAT reporter gene and that the inhibition is not dependent upon other viral genes. Inhibition of CAT expression was due to UL41-dependent reduction of CAT mRNA levels. UL41 alleles encoding polypeptides that lacked vhs activity during virus infections exhibited a similar lack of activity in transfected cells. The results indicate that the UL41 polypeptide is the direct inducer of host mRNA degradation following virus infection and that it is the only virion component directly required for this activity. A 382-amino-acid nonsense polypeptide missing the last 107 residues of UL41 lacked inhibitory activity, but was packaged into virions, while a 343-amino-acid nonsense polypeptide lacked both inhibitory activity and the ability to be packaged.