Document 3300 DOCN M94A3300 TI Effect of human interferon-induced dsRNA-dependent protein kinase on HIV-1 infection. DT 9412 AU Nagai K; Wainberg MA; Geleziunas R; Sonenberg N; Koromillas AE; McGill AIDS Centre, McGill University, Montreal, Qc, Canada. SO Int Conf AIDS. 1994 Aug 7-12;10(1):108 (abstract no. PA0051). Unique Identifier : AIDSLINE ICA10/94369275 AB The interferon (IFN)-induced dsRNA-dependent protein kinase (PKR) is a serine-threonine kinase that displays two distinct kinase activities: i) activation by autophosphorylation, and ii) phosphorylation of the alpha-subunit of eukaryotic initiation factor, elF-2, which causes inhibition of protein synthesis. PKR activation by specific virus RNAs has been suggested to play a key role in the IFN response to viral infection. Infection with human immunodeficiency virus 1 (HIV-1) is associated with the downregulation of PKR which is mediated by the virus-encoded regulatory protein, Tat. We have studied the role of PKR in HIV-1 production using the human monoblastoid cell line U-937 and have established and characterized cell lines expressing a wild-type (wt) human PKR or a dominant negative catalytically inactive PKR mutant (delta 6; deletion of LFIQME residues at position 361 to 366 of the human protein). We found that wt PKR-expressing U-937 cells that were transfected with the HXB2-D clone of HIV-1 produced viral products (reverse transcriptase and p24) more rapidly (7 days vs. 25 days) than did wild-type cells. DE Amino Acid Sequence Cell Line Down-Regulation (Physiology) Enzyme Induction/DRUG EFFECTS Gene Expression Human HIV Infections/*ENZYMOLOGY *HIV-1 Interferons/*PHARMACOLOGY Molecular Sequence Data Protein-Serine-Threonine Kinases/*BIOSYNTHESIS/GENETICS Sequence Deletion Transfection MEETING ABSTRACT SOURCE: National Library of Medicine. NOTICE: This material may be protected by Copyright Law (Title 17, U.S.Code).