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M9620122.TXT
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1996-02-26
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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).