Tipping the balance: antagonism of PKR kinase and ADAR1 deaminase functions by virus gene products.
The protein kinase regulated by RNA (PKR) and the adenosine deaminase acting on RNA (ADAR1) are interferon-inducible enzymes that play important roles in biologic processes including the antiviral actions of interferons, signal transduction, and apoptosis. PKR catalyzes the RNA-dependent phosphorylation of protein synthesis initiation factor eIF-2 alpha, thereby leading to altered translational patterns in interferon-treated and virus-infected cells. PKR also modulates signal transduction responses, including the induction of interferon. ADAR1 catalyzes the deamination of adenosine (A) to generate inosine (I) in RNAs with double-stranded character. Because I is recognized as G instead of A, A-to-I editing by ADAR1 can lead to genetic recoding and altered RNA structures. The importance of PKR and ADAR1 in innate antiviral immunity is illustrated by a number of viruses that encode either RNA or protein viral gene products that antagonize PKR and ADAR1 enzymatic activity, localization, or stability.
George
Cyril X
CX
Department of Molecular, Cellular, and Developmental Biology, University of California, Santa Barbara, California 93106, USA.
Li
Zhiqun
Z
Okonski
Kristina M
KM
Toth
Ann M
AM
Wang
Ying
Y
Samuel
Charles E
CE
D000243:Adenosine Deaminase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D004791:Enzyme Inhibitors / Q000276:immunology / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons / Q000276:immunology; D017393:RNA Editing; D012327:RNA Virus Infections / Q000201:enzymology* / Q000235:genetics* / Q000276:immunology; D012328:RNA Viruses / Q000472:pathogenicity / Q000502:physiology*; D016601:RNA-Binding Proteins; D015398:Signal Transduction; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism; D019892:eIF-2 Kinase / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D004791:Enzyme Inhibitors; D015852:Eukaryotic Initiation Factor-2; D016601:RNA-Binding Proteins; D014764:Viral Proteins; D007372:Interferons; D019892:eIF-2 Kinase; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase