       Document 0246
 DOCN  M95A0246
 TI    High resolution analysis of HIV-1 quasispecies in the brain.
 DT    9510
 AU    Monken CE; Wu B; Srinivasan A; Thomas Jefferson University, Department
       of Microbiology and; Immunology, Philadelphia, Pennsylvania, USA.
 SO    AIDS. 1995 Apr;9(4):345-9. Unique Identifier : AIDSLINE +
 AB    OBJECTIVE: To characterize HIV-1 quasispecies at high resolution to
       determine the in vivo sequence heterogeneity of virus infecting the
       brain. METHODS: A 1 kilobase region of the envelope gene, which includes
       the five hypervariable regions, was amplified by polymerase chain
       reaction (PCR) using DNA obtained from brain tissue of an HIV-1-infected
       patient. PCR products were cloned and 50 clones sequenced. RESULTS:
       Thirty-nine unique nucleotide sequences producing 35 protein variants
       were found. A consensus sequence was identified along with three
       distinct subtypes, each present at a level of 12%. The sequence
       variation from the consensus was 0.1-2.1% at the nucleotide level with
       hypermutation and recombination responsible for the highest diversity.
       Sequence heterogeneity resulted in both the creation and the elimination
       of N-linked glycosylation sites. Only nine clones differed from the
       consensus sequence in the V3 loop. No inactivating mutations were found.
       CONCLUSIONS: HIV-1 proviruses found in the brain generally demonstrate a
       low level of genetic variability in env. However, genomes that vary
       considerably from the predominant species can be present at significant
       levels. This observation may be of importance for understanding viral
       pathogenesis in the central nervous system.
 DE    Amino Acid Sequence  AIDS Dementia Complex/ETIOLOGY/*VIROLOGY  Base
       Sequence  Brain/*VIROLOGY  Cloning, Molecular  DNA Primers/GENETICS
       DNA, Viral/GENETICS  Genes, env  Human  HIV Envelope Protein
       gp120/GENETICS  HIV-1/*GENETICS/*ISOLATION & PURIF/PATHOGENICITY
       Molecular Sequence Data  Polymerase Chain Reaction
       Proviruses/GENETICS/ISOLATION & PURIF  Sequence Homology, Amino Acid
       Support, Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  Variation
       (Genetics)  JOURNAL ARTICLE

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

