ADAR1 interacts with PKR during human immunodeficiency virus infection of lymphocytes and contributes to viral replication.
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.
Clerzius
Guerline
G
Virus-Cell Interactions Laboratory, Lady Davis Institute for Medical Research, McGill University, Montréal, Québec, Canada.
Gélinas
Jean-François
JF
Daher
Aïcha
A
Bonnet
Marion
M
Meurs
Eliane F
EF
Gatignol
Anne
A
D000243:Adenosine Deaminase / Q000235:genetics* / Q000502:physiology*; D020816:Amino Acid Motifs; D002460:Cell Line; D015852:Eukaryotic Initiation Factor-2 / Q000378:metabolism; D015967:Gene Expression Regulation, Viral; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology*; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008214:Lymphocytes / Q000821:virology*; D008954:Models, Biological; D010766:Phosphorylation; D016601:RNA-Binding Proteins; D014162:Transfection; D014779:Virus Replication; D019892:eIF-2 Kinase / Q000378:metabolism*
D015852:Eukaryotic Initiation Factor-2; D016601:RNA-Binding Proteins; D019892:eIF-2 Kinase; C567955:ADARB1 protein, human; D000243:Adenosine Deaminase