The Virion Host Shutoff Function of Herpes Simplex Virus Degrades the 5′ End of a Target mRNA before the 3′ End

During lytic infections, the virion host shutoff (vhs) function of herpes simplex virus (HSV) disaggregates host polysomes and induces rapid turnover of both cellular and viral mRNAs. To examine the steps in vhs-induced mRNA degradation, an RNase protection assay was used to compare the relative decay rates of sequences from the 5′ and 3′ ends of a selected target mRNA. In cells infected with wild-type HSV-1, sequences at the 5′ end of the HSV-1 thymidine kinase mRNA were degraded more rapidly than those at the 3′ end of the transcript. In contrast, in cells infected with a vhs mutant, the decay rates of sequences at the 5′ and 3′ termini of the transcript were much slower and were essentially indistinguishable from each other. Vhs-induced degradation of the transcribed portion of the mRNA was not preceded by detectable shortening of the poly(A) tail in vivo; nor was a poly(A) tail required to make an RNA a target for the vhs activity in vitro. The results suggest that degradation of sequences at or near the 5′ end of an mRNA is an early step in vhs-induced decay.