       Document 0104
 DOCN  M9610104
 TI    The growth advantage conferred by HIV-1 nef is determined at the level
       of viral DNA formation and is independent of CD4 downregulation.
 DT    9601
 AU    Chowers MY; Pandori MW; Spina CA; Richman DD; Guatelli JC; Department of
       Medicine, University of California, San Diego, USA.
 SO    Virology. 1995 Oct 1;212(2):451-7. Unique Identifier : AIDSLINE
       MED/96010217
 AB    Recent data on the phenotype of nef-defective HIV-1 in vitro indicate a
       new function of the Nef gene product: enhancement of viral infectivity.
       Single-cycle replication studies have suggested that Nef enhances the
       efficiency of an early step during viral replication, a step that leads
       to the establishment of viral DNA. To test this interpretation, the
       accumulation of low-molecular-weight (unintegrated) viral DNA was
       measured in cells following exposure to wild-type and nef-defective
       viruses. nef-defective virus accumulated less DNA than the wild type.
       This difference was observed after as little as 5 hr of exposure to
       virus. However, the reverse transcriptase activities of wild-type and
       nef-defective viruses were equal when measured in cell-free assays using
       either exogenous or endogenous templates. In addition, the abilities of
       these viruses to bind and enter cells were not significantly different.
       Together, these data suggest that Nef optimizes postentry events that
       are required for efficient synthesis of viral DNA. To determine if these
       effects were related to the property of Nef-mediated downregulation of
       CD4, growth curves of these viruses were determined using cells that
       express a CD4 molecule unable to respond to Nef. nef-defective virus
       remained attenuated in these cells, indicating that Nef-mediated
       downregulation of CD4 is not required for Nef-mediated enhancement of
       viral propagation in vitro.
 DE    Antigens, CD4/*PHYSIOLOGY  Cell Line  Down-Regulation (Physiology)  DNA,
       Viral/*BIOSYNTHESIS  Gene Products, nef/*PHYSIOLOGY  Human  HIV Core
       Protein p24/BIOSYNTHESIS  HIV-1/*GROWTH & DEVELOPMENT/METABOLISM
       RNA-Directed DNA Polymerase/METABOLISM  Support, U.S. Gov't, Non-P.H.S.
       Support, U.S. Gov't, P.H.S.  Virus Replication  JOURNAL ARTICLE

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

