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).