Full resistance of herpes simplex virus type 1-infected primary human cells to alpha interferon requires both the Us11 and gamma(1)34.5 gene products.
The gamma(1)34.5 gene product is important for the resistance of herpes simplex virus type 1 (HSV-1) to interferon. However, since the inhibition of protein synthesis observed in cells infected with a gamma(1)34.5 mutant virus results from the combined loss of the gamma(1)34.5 gene product and the failure to translate the late Us11 mRNA, we sought to characterize the relative interferon sensitivity of mutants unable to produce either the Us11 or the gamma(1)34.5 polypeptide. We now demonstrate that primary human cells infected with a Us11 mutant virus are hypersensitive to alpha interferon, arresting translation upon entry into the late phase of the viral life cycle. Furthermore, immediate-early expression of Us11 by a gamma(1)34.5 deletion mutant is sufficient to render translation resistant to alpha interferon. Finally, we establish that the Us11 gene product is required for wild-type levels of replication in alpha interferon-treated cells and, along with the gamma(1)34.5 gene, is an HSV-1-encoded interferon resistance determinant.
Department of Microbiology-MSB 214, New York University School of Medicine, 550 First Ave., New York, NY 10016, USA.
Matthew
M
Mulvey
Vladimir
V
Camarena
Ian
I
Mohr
D002478:Cells, Cultured; D024882:Drug Resistance, Viral / Q000235:genetics; D017353:Gene Deletion; D015870:Gene Expression; D005814:Genes, Viral; D018259:Herpesvirus 1, Human / Q000187:drug effects* / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D014176:Protein Biosynthesis / Q000187:drug effects; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D011994:Recombinant Proteins; D014764:Viral Proteins / Q000235:genetics* / Q000502:physiology; D014779:Virus Replication / Q000187:drug effects
D007370:Interferon Type I; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; C074546:US11 protein, herpesvirus; D014764:Viral Proteins; C066469:gamma 34.5 protein, Human herpesvirus 1