Inhibition of the interferon-inducible protein kinase PKR by HCV E2 protein.
Most isolates of hepatitis C virus (HCV) infections are resistant to interferon, the only available therapy, but the mechanism underlying this resistance has not been defined. Here it is shown that the HCV envelope protein E2 contains a sequence identical with phosphorylation sites of the interferon-inducible protein kinase PKR and the translation initiation factor eIF2alpha, a target of PKR. E2 inhibited the kinase activity of PKR and blocked its inhibitory effect on protein synthesis and cell growth. This interaction of E2 and PKR may be one mechanism by which HCV circumvents the antiviral effect of interferon.
Taylor
D R
DR
Department of Molecular Microbiology and Immunology and Howard Hughes Medical Institute, University of Southern California, School of Medicine, Los Angeles, CA 90089, USA.
Shi
S T
ST
Romano
P R
PR
Barber
G N
GN
Lai
M M
MM
D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis; D004352:Drug Resistance, Microbial; D004721:Endoplasmic Reticulum / Q000378:metabolism; D004790:Enzyme Induction; D015852:Eukaryotic Initiation Factor-2 / Q000737:chemistry / Q000378:metabolism; D006367:HeLa Cells; D016174:Hepacivirus / Q000187:drug effects; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011993:Recombinant Fusion Proteins / Q000378:metabolism / Q000494:pharmacology; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D014162:Transfection; D014170:Transformation, Genetic; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
D015852:Eukaryotic Initiation Factor-2; D016898:Interferon-alpha; D011993:Recombinant Fusion Proteins; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus; D015500:Chloramphenicol O-Acetyltransferase; D019892:eIF-2 Kinase