Early shutoff of host protein synthesis in cells infected with herpes simplex viruses.
Herpes simplex viruses 1 (HSV-1) and 2 (HSV-2) are capable of suppressing the host cell protein synthesis even without viral gene expression. This phenomenon is known as the early shutoff or as the virion-associated host shutoff (vhs) to emphasize that it is mediated by a component of infecting virions which is a product of the UL41 (vhs) gene. The UL41 encoded protein is a functional tegument protein also present in light (L) particles and is not essential for virus replication. The major product of UL41 gene is a 58 K phosphoprotein. At least two forms of UL41 protein differing in the extent of phosphorylation are present in HSV-1-infected cells. HSV-2 compared to HSV-1 strains display a stronger vhs phenotype. However, in superinfection experiments the less strong vhs phenotype is dominant. UL41 protein triggers disruption of polysomes and rapid degradation of all host and viral mRNAs and blocks a reporter gene expression without other HSVs proteins. The available evidence suggests that UL41 protein is either itself a ribonuclease (RNase) or a subunit of RNase that contains also one or more cellular subunits. UL41 protein is capable of interacting with a transactivator of an alpha-gene, the alpha-transinducing factor (alpha-TIF). Interaction of UL41 protein with alpha-TIF down regulates the UL41 (vhs) gene activity during lytic infection. The possible role of other viral proteins in the shutoff is discussed.
Matis
J
J
Institute of Virology, Slovak Academy of Sciences, Bratislava. virumati@nic.savba.sk
Kúdelová
M
M
D002460:Cell Line; D006561:Herpes Simplex / Q000276:immunology / Q000378:metabolism* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000472:pathogenicity*; D018258:Herpesvirus 2, Human / Q000472:pathogenicity*; D006801:Humans; D008957:Models, Genetic; D009154:Mutation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000737:chemistry; D012260:Ribonucleases; D012680:Sensitivity and Specificity; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014779:Virus Replication
D012333:RNA, Messenger; D014764:Viral Proteins; C070722:virion host shutoff protein, Simplexvirus; D012260:Ribonucleases