Infected Cell Protein 22 of Herpes Simplex Virus 1 Regulates the Expression of Virion Host Shutoff Gene UL41

Abstract

The UL41 protein of herpes simplex virus 1 (HSV-1) is packaged into virions, and in newly infected cells the protein mediates indiscriminate degradation of mRNA, which causes a shutoff of protein synthesis. We report that in cells infected with mutant virus in which either α22/US1.5 or UL13 had been deleted: (i) the shutoff of protein synthesis and the degradation of mRNA did not take place or were greatly reduced, and consistent with these observations (ii) cells infected with mutant viruses accumulated less UL41 mRNA and protein than cells infected with the parent virus; and (iii) purified virions from cells infected with ΔUL13 or Δα22/ΔUS1.5 viruses contained less UL41 protein than virions produced by the wild-type parent virus. We conclude that the failure of the UL13−mutant virus to shut off protein synthesis immediately after infection is due to the failure of posttranslational modification of infected cell protein 22 and/or the related US1.5 protein by the UL13 protein kinase. The regulatory effect of UL13 on UL41 is indirect and not contingent on direct interaction of this protein with the UL41 protein.