ADAR1 and PACT contribute to efficient translation of transcripts containing HIV-1 trans-activating response (TAR) element.
Human immunodeficiency virus type 1 (HIV-1) has evolved various measures to counter the host cell's innate antiviral response during the course of infection. Interferon (IFN)-stimulated gene products are produced following HIV-1 infection to limit viral replication, but viral proteins and RNAs counteract their effect. One such mechanism is specifically directed against the IFN-induced Protein Kinase PKR, which is centrally important to the cellular antiviral response. In the presence of viral RNAs, PKR is activated and phosphorylates the translation initiation factor eIF2α. This shuts down the synthesis of both host and viral proteins, allowing the cell to mount an effective antiviral response. PACT (protein activator of PKR) is a cellular protein activator of PKR, primarily functioning to activate PKR in response to cellular stress. Recent studies have indicated that during HIV-1 infection, PACT's normal cellular function is compromised and that PACT is unable to activate PKR. Using various reporter systems andin vitrokinase assays, we establish in this report that interactions between PACT, ADAR1 and HIV-1-encoded Tat protein diminish the activation of PKR in response to HIV-1 infection. Our results highlight an important pathway by which HIV-1 transcripts subvert the host cell's antiviral activities to enhance their translation.
Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, U.S.A.
Evelyn
E
Chukwurah
Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, U.S.A.
Indhira
I
Handy
Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, U.S.A. patelr@biol.sc.edu.
Rekha C
RC
Patel
D000243:Adenosine Deaminase / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics* / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000821:virology; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D057809:HEK293 Cells; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D054884:Host-Pathogen Interactions; D006801:Humans; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D014176:Protein Biosynthesis; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D019892:eIF-2 Kinase / Q000235:genetics* / Q000378:metabolism; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000378:metabolism
D015852:Eukaryotic Initiation Factor-2; C104647:PRKRA protein, human; D016601:RNA-Binding Proteins; D054322:tat Gene Products, Human Immunodeficiency Virus; D008156:Luciferases; C000602769:EIF2AK2 protein, human; D019892:eIF-2 Kinase; C000595356:ADAR protein, human; D000243:Adenosine Deaminase
ADAR1; HIV-1; PACT; PKR; Tat; interferons