Temperature-sensitive mutations in the putative herpes simplex virus type 1 terminase subunits pUL15 and pUL33 preclude viral DNA cleavage/packaging and interaction with pUL28 at the nonpermissive temperature.

Terminases comprise essential components of molecular motors required to package viral DNA into capsids in a variety of DNA virus systems. Previous studies indicated that the herpes simplex virus type 1 U(L)15 protein (pU(L)15) interacts with the pU(L)28 moiety of a pU(L)28-pU(L)33 complex to form the likely viral terminase. In the current study, a novel temperature-sensitive mutant virus was shown to contain a mutation in U(L)33 codon 61 predicted to change threonine to proline.

Mapping of key functions of the herpes simplex virus 1 U(S)3 protein kinase: the U(S)3 protein can form functional heteromultimeric structures derived from overlapping truncated polypeptides.

Earlier studies have shown that the herpes simplex virus (HSV) U(S)3 encodes two transcriptional units directing the synthesis of the U(S)3 (residues 1 to 481) and U(S)3.5 (residues 77 to 481) protein kinases. Both kinases phosphorylate histone deacetylase 1 (HDAC1) and HDAC2 and enable the expression of genes cotransduced into U2OS cells by recombinant baculoviruses, an activity designated the "helper function.

ICP0 and the US3 protein kinase of herpes simplex virus 1 independently block histone deacetylation to enable gene expression.

SK-N-SH cells exposed to low ratios of ICP0-null (DeltaICP0) mutants of herpes simplex virus per cell express the viral alpha proteins, but the progression to beta and gamma gene expression does not ensue. In these restrictive cells, post-alpha gene expression can be induced after exposure of the infected cells to sodium butyrate, an indication that VP16 brought into cells by the virus and the alpha gene products made after infection cannot block the silencing of viral post-alpha genes by histone deacetylases (HDACs). This observation is consistent with evidence reported earlier that ICP0 dissociates HDAC1/2 from the CoREST/REST complex.

U(S)3 and U(S)3.5 protein kinases of herpes simplex virus 1 differ with respect to their functions in blocking apoptosis and in virion maturation and egress.

Previously, we reported that the U(S)3 protein kinase blocks apoptosis, that it activates protein kinase A (PKA), that activation of PKA blocks apoptosis in cells infected with a U(S)3 deletion mutant, and that an overlapping transcriptional unit encodes a truncated kinase designated U(S)3.5. Here, we report the properties of the kinases based on comparisons of herpes simplex virus and baculoviruses expressing U(S)3 or U(S)3.

Ionizing radiation activates late herpes simplex virus 1 promoters via the p38 pathway in tumors treated with oncolytic viruses.

Ionizing radiation potentiates the oncolytic activity of attenuated herpes simplex viruses in tumors exposed to irradiation at specific time intervals by inducing higher virus yields. Cell culture studies have shown that an attenuated virus lacking the viral gamma(1)34.5 genes underproduces late proteins whose synthesis depends on sustained synthesis of viral DNA.

Herpes simplex virus 1 ICP22 regulates the accumulation of a shorter mRNA and of a truncated US3 protein kinase that exhibits altered functions.

The U(S)3 open reading frame of herpes simplex virus 1 (HSV-1) was reported to encode two mRNAs each directing the synthesis of the same protein. We report that the U(S)3 gene encodes two proteins. The predominant U(S)3 protein is made in wild-type HSV-1-infected cells.

The carboxyl-terminal domain of RNA polymerase II is phosphorylated by a complex containing cdk9 and infected-cell protein 22 of herpes simplex virus 1.

The infected-cell protein 22 (ICP22), a regulatory protein encoded by the alpha22 gene of herpes simplex virus 1, is required for the optimal expression of a set of late viral proteins that includes the products of the U(S)11, U(L)38, and U(L)41 genes. ICP22 has two activities. Thus, ICP22 and the U(L)13 protein kinase mediate the activation of cdc2 and degradation of its partners, cyclins A and B.

Herpes simplex virus 1 gene expression is accelerated by inhibitors of histone deacetylases in rabbit skin cells infected with a mutant carrying a cDNA copy of the infected-cell protein no. 0.

An earlier report showed that the expression of viral genes by a herpes simplex virus 1 mutant [HSV-1(vCPc0)] in which the wild-type, spliced gene encoding infected-cell protein no. 0 (ICP0) was replaced by a cDNA copy is dependent on both the cell type and multiplicity of infection. At low multiplicities of infection, viral gene expression in rabbit skin cells was delayed by many hours, although ultimately virus yield was comparable to that of the wild-type virus.

An early regulatory function required in a cell type-dependent manner is expressed by the genomic but not the cDNA copy of the herpes simplex virus 1 gene encoding infected cell protein 0.

The alpha 0 genes of herpes simplex virus 1 (HSV-1) contain three exons. Earlier studies have shown that the substitution of genomic sequences with a cDNA copy does not alter the capacity of the virus to replicate or establish latent infection. Other studies have demonstrated that HSV-1 may express alternatively spliced forms of alpha 0 transcripts.

Of the three tegument proteins that package mRNA in herpes simplex virions, one (VP22) transports the mRNA to uninfected cells for expression prior to viral infection.

An earlier report has shown that herpes simplex virus 1 virions package RNA. Experiments designed to reveal the identity of the virion proteins capable of binding the RNA and to show whether the mRNA carried in the newly infected cells was expressed showed the following: (i) (32)P-labeled riboprobe generated by in vitro transcription of the U(S)8.5 ORF bound three proteins identified as the products of U(S)11, U(L)47, and U(L)49 (VP22) genes.

U(S)3 protein kinase of herpes simplex virus 1 blocks caspase 3 activation induced by the products of U(S)1.5 and U(L)13 genes and modulates expression of transduced U(S)1.5 open reading frame in a cell type-specific manner.

The coding domain of the herpes simplex virus type 1 (HSV-1) alpha22 gene encodes two proteins, the 420-amino-acid infected-cell protein 22 (ICP22) and U(S)1.5, a protein colinear with the carboxyl-terminal domain of ICP22. In HSV-1-infected cells, ICP22 and U(S)1.