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M94A3300.TXT
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1994-10-25
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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).