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ADAR1 interacts with PKR during human immunodeficiency virus infection of lymphocytes and contributes to viral replication.

Abstract : 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.
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Submitted on : Monday, March 1, 2010 - 3:14:35 PM
Last modification on : Thursday, June 18, 2020 - 12:32:04 PM

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Guerline Clerzius, Jean-François Gélinas, Aïcha Daher, Marion Bonnet, Eliane F. Meurs, et al.. ADAR1 interacts with PKR during human immunodeficiency virus infection of lymphocytes and contributes to viral replication.. Journal of Virology, American Society for Microbiology, 2009, 83 (19), pp.10119-28. ⟨10.1128/JVI.02457-08⟩. ⟨pasteur-00460530⟩

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