       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).

