Infected cell protein 22 of herpes simplex virus 1 regulates the expression of virion host shutoff gene U(L)41.

The U(L)41 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 alpha22/U(S)1.5 or U(L)13 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 U(L)41 mRNA and protein than cells infected with the parent virus; and (iii) purified virions from cells infected with deltaU(L)13 or delta alpha22/deltaU(S)1.5 viruses contained less U(L)41 protein than virions produced by the wild-type parent virus. We conclude that the failure of the U(L)13- 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 U(S)1.5 protein by the U(L)13 protein kinase. The regulatory effect of U(L)13 on U(L)41 is indirect and not contingent on direct interaction of this protein with the U(L)41 protein.