       Document 0519
 DOCN  M9620519
 TI    Extracellular Nef protein regulates productive HIV-1 infection from
       latency.
 DT    9602
 AU    Fujinaga K; Zhong Q; Nakaya T; Kameoka M; Meguro T; Yamada K; Ikuta K;
       Section of Serology, Hokkaido University, Kita-ku, Sapporo,; Japan.
 SO    J Immunol. 1995 Dec 1;155(11):5289-98. Unique Identifier : AIDSLINE
       MED/96072805
 AB    In HIV-1-infected asymptomatic carriers, the vast majority of infected
       cells in PBMCs are believed to be latently or nonproductively infected.
       We have isolated a subclone (MOLT-20-2) from an infected T cell line
       that expressed HIV-1 Ags at a very low level. However, viral Ag
       expression was markedly up-regulated by stimulation with either
       TNF-alpha, A23187, or PMA, indicating that the subclone might provide a
       suitable model of HIV-1 latency. Our previous studies have shown that
       the carboxyl-terminal region of the extracellular form of HIV-1 Nef
       played an important role in the interaction of infected cells with
       uninfected T cells, and could induce the cytostatic state. This
       suggested that Nef might contribute to intracellular signal transduction
       through an interaction with latently infected cells. We show in this
       study that stimulation of MOLT-20-2 with soluble Nef leads to HIV-1
       activation from latency in a dose-dependent manner. Moreover, using a
       total of 14 overlapping Nef-related synthetic peptides, stimulatory
       activity was mapped to a discrete peptide (amino acid residues 132-147)
       that had the potential to activate latent HIV-1. This novel Nef function
       was confirmed by activation of virus production from the PBMCs of
       asymptomatic carriers. In addition, Nef-dependent HIV-1 activation from
       latency was also observed in another independently derived, latently
       infected cell line, U1, though not in cell line ACH-2. These results
       extend the significance of the Nef activity in vivo to the regulation of
       productive HIV-1 infection from latency, and define the regions of the
       protein involved.
 DE    Amino Acid Sequence  Antibodies, Monoclonal/IMMUNOLOGY  Antigens,
       CD4/IMMUNOLOGY  Base Sequence  Calcimycin/PHARMACOLOGY  Cell Line
       CD4-Positive T-Lymphocytes/VIROLOGY  DNA Primers  Gene Products,
       nef/*PHARMACOLOGY  Human  HIV-1/*DRUG EFFECTS/GROWTH & DEVELOPMENT
       Models, Biological  Molecular Sequence Data  Support, Non-U.S. Gov't
       Tetradecanoylphorbol Acetate/PHARMACOLOGY  Tumor Necrosis
       Factor/IMMUNOLOGY/PHARMACOLOGY  *Virus Activation  Virus Latency
       JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

