Human cytomegalovirus TRS1 and IRS1 gene products block the double-stranded-RNA-activated host protein shutoff response induced by herpes simplex virus type 1 infection.
Human cytomegalovirus (HCMV) attachment and entry stimulates the expression of cellular interferon-inducible genes, many of which target important cellular functions necessary for viral replication. Double-stranded RNA-dependent host protein kinase (PKR) is an interferon-inducible gene product that limits viral replication by inhibiting protein translation in the infected cell. It was anticipated that HCMV encodes gene products that facilitate the evasion of this PKR-mediated antiviral response. Using a deltagamma1 34.5 herpes simplex virus type 1 (HSV-1) recombinant that triggers PKR-mediated protein synthesis shutoff, experiments identified an HCMV gene product expressed in the initial hours of infection that allows continued protein synthesis in the infected cell. Recombinant HSV-1 viruses expressing either the HCMV TRS1 or IRS1 protein demonstrate that either of these HCMV gene products allows the deltagamma1 34.5 recombinant viruses to evade PKR-mediated protein shutoff and maintain late viral protein synthesis.
UAB Department of Pediatrics, 1600 6th Avenue South, CHB-118C, Birmingham, AL 35233, USA. kcassady@peds.uab.edu
Kevin A
KA
Cassady
D000818:Animals; D002522:Chlorocebus aethiops; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D005838:Genotype; D006561:Herpes Simplex / Q000378:metabolism* / Q000821:virology; D018259:Herpesvirus 1, Human; D006801:Humans; D010766:Phosphorylation; D014176:Protein Biosynthesis; D014709:Vero Cells; D014764:Viral Proteins / Q000502:physiology*; D019892:eIF-2 Kinase / Q000502:physiology*
D015852:Eukaryotic Initiation Factor-2; C072216:TRS1 protein, Human herpesvirus 5; D014764:Viral Proteins; D019892:eIF-2 Kinase