ADAR1 interacts with PKR during human immunodeficiency virus infection of lymphocytes and contributes to viral replication
| Autor: | Aïcha Daher, Marion C. Bonnet, Eliane F. Meurs, Guerline Clerzius, Jean-François Gélinas, Anne Gatignol |
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| Přispěvatelé: | Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, Department of Experimental Medicine, McGill University = Université McGill [Montréal, Canada], Department of Microbiology and Immunology [Montréal], Hépacivirus et immunité innée, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
MESH: Eukaryotic Initiation Factor-2
Adenosine Deaminase viruses Amino Acid Motifs Eukaryotic Initiation Factor-2 HIV Infections Virus Replication Jurkat cells MESH: HIV-1 Jurkat Cells eIF-2 Kinase MESH: Amino Acid Motifs MESH: Gene Expression Regulation Viral MESH: Jurkat Cells Lymphocytes Phosphorylation MESH: Adenosine Deaminase 0303 health sciences 030302 biochemistry & molecular biology RNA-Binding Proteins virus diseases Transfection MESH: HIV Infections Genome Replication and Regulation of Viral Gene Expression 3. Good health [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology Gene Expression Regulation Viral Immunology Biology Models Biological Microbiology Virus Cell Line MESH: eIF-2 Kinase 03 medical and health sciences Virology Humans Protein kinase A 030304 developmental biology EIF-2 kinase MESH: Humans MESH: Phosphorylation MESH: Transfection MESH: Virus Replication MESH: Models Biological RNA Protein kinase R MESH: Cell Line Viral replication Insect Science HIV-1 biology.protein MESH: Lymphocytes |
| Zdroj: | Journal of Virology Journal of Virology, American Society for Microbiology, 2009, 83 (19), pp.10119-28. ⟨10.1128/JVI.02457-08⟩ Journal of Virology, 2009, 83 (19), pp.10119-28. ⟨10.1128/JVI.02457-08⟩ |
| ISSN: | 0022-538X 1098-5514 |
| DOI: | 10.1128/JVI.02457-08⟩ |
| Popis: | The interferon-induced protein kinase RNA activated (PKR) is activated after virus infection. This activation is transient during the human immunodeficiency virus type 1 (HIV-1) infection of lymphocytes, and the protein is not activated at the peak of infection. We observed that interferon-induced adenosine deaminase acting on RNA 1-p150 (ADAR1-p150) and ADAR1-p110 expression increases while the virus replicates actively. Furthermore, both forms of ADAR1 show enhanced interactions with PKR at the peak of HIV infection, suggesting a role for this protein in the regulation of PKR activation. We observed that ADAR1-p150, as previously shown for the TAR RNA binding protein (TRBP), reverses the PKR inhibition of HIV expression and production in HEK 293T cells. This activity requires the Z-DNA binding motif and the three double-stranded RNA binding domains but not the catalytic domain. In astrocytic cells, ADAR1-p150 increased HIV expression and production to an extent similar to that of TRBP. Small interfering RNAs against ADAR1-p150 moderately decreased HIV production. These results indicate that two interferon-induced proteins, ADAR1 and PKR, have antagonistic functions on HIV production. They suggest that ADAR1 and TRBP belong to a multiprotein complex that inhibits PKR during the HIV infection of lymphocytes. |
| Databáze: | OpenAIRE |
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