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M9460201.TXT
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1994-06-12
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Document 0201
DOCN M9460201
TI Distinct effects in primary macrophages and lymphocytes of the human
immunodeficiency virus type 1 accessory genes vpr, vpu, and nef:
mutational analysis of a primary HIV-1 isolate.
DT 9408
AU Balliet JW; Kolson DL; Eiger G; Kim FM; McGann KA; Srinivasan A; Collman
R; Department of Medicine (Pulmonary and Critical Care Division),;
University of Pennsylvania School of Medicine, Philadelphia; 19104-6076.
SO Virology. 1994 May 1;200(2):623-31. Unique Identifier : AIDSLINE
MED/94233725
AB Macrophages and lymphocytes are the two main targets for productive
HIV-1 infection in vivo. To compare the effects of the nonessential
HIV-1 accessory genes vpr, vpu, and nef on viral replication in these
primary cell types, we generated a panel of mutant viruses derived from
a molecularly cloned macrophage-tropic HIV-1 primary isolate. Mutant
viruses had markedly different patterns of replication in macrophages,
in contrast to lymphocytes in which differences were modest. Loss of vpr
or vpu reduced viral antigen production in macrophages by up to
1000-fold, while replication in lymphocytes was only marginally
affected. Loss of nef did not affect lymphocyte infection, but decreased
replication in macrophages to a small extent. Mutation of multiple
accessory genes restricted replication in both cell types, but to a much
greater extent in macrophages, and frequently resulted in nonproductive
infection. The degree to which replication depended on intact accessory
genes varied in macrophages from different donors. The essential
functions of these accessory genes in HIV-1 infection may be related to
their combined effects in facilitating productive infection of
macrophages.
DE Base Sequence Comparative Study DNA Mutational Analysis Genes,
nef/GENETICS Genes, vpr/GENETICS Genes, vpu/GENETICS Genes,
Viral/*GENETICS Human HIV-1/*GROWTH & DEVELOPMENT/GENETICS
Lymphocytes/*MICROBIOLOGY Macrophages/*MICROBIOLOGY Molecular Sequence
Data Mutagenesis Proviruses/GENETICS Support, Non-U.S. Gov't
Support, U.S. Gov't, P.H.S. Virus Replication/GENETICS JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).