       Document 0122
 DOCN  M9620122
 TI    Both virus and host components are important for the manifestation of a
       Nef- phenotype in HIV-1 and HIV-2.
 DT    9602
 AU    Ryan-Graham MA; Peden KW; Laboratory of Molecular Microbiology, NIAID,
       NIH, Bethesda,; Maryland 20892, USA.
 SO    Virology. 1995 Oct 20;213(1):158-68. Unique Identifier : AIDSLINE
       MED/96036490
 AB    While it has been demonstrated that the Nef protein of simian
       immunodeficiency virus is obligatory for the establishment of high viral
       loads and the development of simian AIDS in rhesus macaques,
       demonstrating a critical role for the human immunodeficiency virus (HIV)
       Nef protein in tissue culture has been elusive. Data have been
       contradictory as to whether Nef has a negative or positive influence on
       in vitro virus replication. In an attempt to define a role for Nef
       during virus propagation in tissue culture and to obtain virus-host
       systems that could distinguish between the Nef mutant and wild-type
       viruses, we have introduced mutations into the nef genes of infectious
       molecular clones of three HIV-1 strains and two isolates of the HIV-2ROD
       strain and have investigated the capacity of viruses derived from them
       to infect a number of CD4-positive T-cell lines and peripheral blood
       mononuclear cells (PBMC). Mutating the nef gene of all viruses had a
       modest negative effect on virus production in activated PBMC. In some
       T-cell lines with some viruses, the effects were severe, and little or
       no Nef mutant virus could be detected. In other cell lines, the result
       of mutating the nef gene either had no effect or had a slight negative
       effect on the replication kinetics. Therefore, whether the consequences
       of loss of Nef activity can be demonstrated in vitro depends on both the
       particular virus and the host cell used, suggesting that Nef is exerting
       its activity on some cellular pathway. In addition, we describe the
       construction and properties of hitherto unreported infectious molecular
       clones of the ROD strain of HIV-2.
 DE    Amino Acid Sequence  Base Sequence  Cell Line  Cells, Cultured
       CD4-Positive T-Lymphocytes/VIROLOGY  DNA, Viral/ANALYSIS  Frameshift
       Mutation  Gene Products, nef/GENETICS/*PHYSIOLOGY  Genes, nef/GENETICS
       Human  HIV-1/GENETICS/*PHYSIOLOGY  HIV-2/GENETICS/*PHYSIOLOGY
       Kidney/CYTOLOGY  Leukocytes, Mononuclear/VIROLOGY  Molecular Sequence
       Data  Open Reading Frames  Phenotype  Support, Non-U.S. Gov't  Support,
       U.S. Gov't, P.H.S.  Transfection  Virus Replication/PHYSIOLOGY  JOURNAL
       ARTICLE

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

