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

Clerzius, Guerline, Gelinas, Jean-Francois, Daher, Aicha, Bonnet, Marion ORCID: https://orcid.org/0000-0002-7559-2413, Meurs, Eliane and Gatignol, Anne 2009. ADAR1 interacts with PKR during human immunodeficiency virus infection of lymphocytes and contributes to viral replication. Journal of Virology 83 , pp. 10119-10128. 10.1128/JVI.02457-08

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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.

Item Type:	Article
Date Type:	Published Online
Status:	Published
Schools:	Medicine
Publisher:	American Society for Microbiology
ISSN:	0022-538X
Date of First Compliant Deposit:	16 November 2020
Date of Acceptance:	9 July 2009
Last Modified:	15 Nov 2023 10:16
URI:	https://orca.cardiff.ac.uk/id/eprint/136372

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