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M9490405.TXT
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1994-09-19
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Document 0405
DOCN M9490405
TI In vivo distribution and cytopathology of variants of human
immunodeficiency virus type 1 showing restricted sequence variability in
the V3 loop.
DT 9411
AU Donaldson YK; Bell JE; Holmes EC; Hughes ES; Brown HK; Simmonds P;
Department of Medical Microbiology, University of Edinburgh,; Medical
School, United Kingdom.
SO J Virol. 1994 Sep;68(9):5991-6005. Unique Identifier : AIDSLINE
GENBANK/L34441
AB The distribution, cell tropism, and cytopathology in vivo of human
immunodeficiency virus (HIV) was investigated in postmortem tissue
samples from a series of HIV-infected individuals who died either of
complications associated with AIDS or for unrelated reasons while they
were asymptomatic. Proviral sequences were detected at a high copy
number in lymphoid tissue of both presymptomatic patients and patients
with AIDS, whereas significant infection of nonlymphoid tissue such as
that from brains, spinal cords, and lungs were confined to those with
AIDS. V3 loop sequences from both groups showed highly restricted
sequence variability and a low overall positive charge of the encoded
amino acid sequence compared with those of standard laboratory isolates
of HIV type 1 (HIV-1). The low charge and the restriction in sequence
variability were comparable to those observed with isolates showing a
non-syncytium-inducing (NSI) and macrophage-tropic phenotype in vitro.
All patients were either exclusively infected (six of seven cases) or
predominantly infected (one case) with variants with a predicted
NSI/macrophage-tropic phenotype, irrespective of the degree of disease
progression. p24 antigen was detected by immunocytochemical staining of
paraffin-fixed sections in the germinal centers within lymphoid tissue,
although little or no antigen was found in areas of lymph node or spleen
containing T lymphocytes from either presymptomatic patients or patients
with AIDS. The predominant p24 antigen-expressing cells in the lungs and
brains of the patients with AIDS were macrophages and microglia (in
brains), frequently forming multinucleated giant cells (syncytia) even
though the V3 loop sequences of these variants resembled those of NSI
isolates in vitro. These studies indicate that lack of syncytium-forming
ability in established T-cell lines does not necessarily predict
syncytium-forming ability in primary target cells in vivo. Furthermore,
variants of HIV with V3 sequences characteristic of
NSI/macrophage-tropic isolates form the predominant population in a
range of lymphoid and nonlymphoid tissues in vivo, even in patients with
AIDS.
DE Acquired Immunodeficiency Syndrome/MICROBIOLOGY Amino Acid Sequence
Base Sequence Comparative Study DNA Primers/CHEMISTRY Genes, pol
Human HIV Envelope Protein gp120/*CHEMISTRY HIV
Infections/*MICROBIOLOGY HIV-1/*PATHOGENICITY Macrophages/MICROBIOLOGY
Molecular Sequence Data Phylogeny Proviruses/CHEMISTRY Sequence
Alignment Sequence Homology, Amino Acid Support, Non-U.S. Gov't
T-Lymphocytes/MICROBIOLOGY Variation (Genetics) JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).