       Document 0796
 DOCN  M9590796
 TI    Human immunodeficiency virus type 1 Nef increases the efficiency of
       reverse transcription in the infected cell.
 DT    9509
 AU    Schwartz O; Marechal V; Danos O; Heard JM; Laboratoire Retrovirus et
       Transfert Genetique, Institut; Pasteur, Paris, France.
 SO    J Virol. 1995 Jul;69(7):4053-9. Unique Identifier : AIDSLINE
       MED/95287454
 AB    We have analyzed the replication of Nef+ and Nef- isogenic human
       immunodeficiency virus in CEM, HUT78, MT4 lymphoid, and U937 monocytic
       cell lines. At each passage of infected cells, we have assessed the
       relative infectivity of the virus particles released in culture media by
       measuring the number of infections units per nanogram of p24 protein.
       Values appeared to be 3- to 10-fold higher for the Nef+ virus than for
       the Nef- number The positive effect of Nef was observed regardless of
       the cell line, the multiplicity of infection, and the number of virus
       replication cycles achieved. We showed, by using cells expressing
       glycosylphosphatidylinositol-linked CD4, that the enhancement of virion
       infectivity could be dissociated from the down-regulation of cell
       surface CD4 also induced by Nef. The gp120-to-p24 ratio and the RNA
       content of virus particles produced in the presence or in the absence of
       Nef were equivalent. Virions bound to cell surface CD4 receptors with
       equal efficiencies. Equivalent reverse transcriptase activities were
       measured both on exogenous substrate and on particle genomic RNAs. In
       contrast, reverse transcription in infected cells generated 5- to
       10-fold less DNA when the virions were produced in the absence of Nef,
       indicating that these particles performed reverse transcription in a
       suboptimal environment. These data suggest that the expression of Nef in
       virus-producing cells is required for efficient processing of the early
       stages of virus replication in target cells, including the
       internalization in an appropriate cell compartment and the uncoating of
       the particle.
 DE    Cell Line  DNA, Viral/*BIOSYNTHESIS  Gene Products, nef/*PHYSIOLOGY
       Human  HIV-1/*PHYSIOLOGY  Reverse Transcriptase/*METABOLISM  RNA,
       Viral/ANALYSIS  Support, Non-U.S. Gov't  Virus Replication  JOURNAL
       ARTICLE

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

