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M9640572.TXT
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1996-03-04
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Document 0572
DOCN M9640572
TI In vivo processing of Pr160gag-pol from human immunodeficiency virus
type 1 (HIV) in acutely infected, cultured human T-lymphocytes.
DT 9604
AU Lindhofer H; von der Helm K; Nitschko H; Max von Pettenkofer-Institute,
University of Munich, Germany.
SO Virology. 1995 Dec 20;214(2):624-7. Unique Identifier : AIDSLINE
MED/96130203
AB The processing of the HIV-1 Pr160gag-pol precursor polyprotein was
analyzed in freshly HIV-1-infected MT-4 cultured cells. Single
intermediates of the processing cascade were characterized by
immunoblotting using distinct antisera. A potent inhibitor of the HIV
protease (PR), Ro 31-8959, was employed to block cleavage by the mature
PR, thus allowing insights into initial stages of the gag-pol
(auto)-catalytical processing. While most known gag-pol cleavages were
blocked in the presence of the inhibitor, the cleavage site between the
gag-NC and the pol-p6 domains was still cleaved even in presence of high
amounts (1 microM) of inhibitor, leading to the accumulation of a novel
114-kDa polyprotein comprising p6-PR-RT-IN. In the absence of inhibitor
no accumulation of p114 was observed. In inhibitor-treated,
HIV-1-infected cells a p6-PR intermediate was also detected, indicating
subsequent cleavage of the PR/RT scissile bond. These results
demonstrate initial cleavage(s) of the gag-pol precursor hydrolyzed by a
proteolytic activity different from the mature PR and indicate that p114
(p6-PR-RT-IN) and p6-PR intermediates could play an essential role in
the PR activation process.
DE Binding Sites Cell Line Enzyme Precursors/METABOLISM Gene Products,
gag/*METABOLISM Human HIV Protease/METABOLISM HIV Protease
Inhibitors/PHARMACOLOGY Isoquinolines/PHARMACOLOGY Protein
Precursors/*METABOLISM *Protein Processing, Post-Translational
Quinolines/PHARMACOLOGY Substrate Specificity Support, Non-U.S. Gov't
T-Lymphocytes/*VIROLOGY JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).