       Document 0795
 DOCN  M9610795
 TI    Distinct HIV-1 long terminal repeat quasispecies present in nervous
       tissues compared to that in lung, blood and lymphoid tissues of an AIDS
       patient.
 DT    9601
 AU    Ait-Khaled M; McLaughlin JE; Johnson MA; Emery VC; Department of
       Virology, Royal Free Hospital, London, UK.
 SO    AIDS. 1995 Jul;9(7):675-83. Unique Identifier : AIDSLINE MED/96035228
 AB    OBJECTIVE: To investigate the phylogenetic relationship of HIV-1
       proviral long terminal repeat (LTR) variants present in postmortem
       samples of lymph node, spleen, lung, dorsal root ganglion and spinal
       cord as well as in the peripheral blood of an HIV-1-infected patient
       dying with AIDS. DESIGN AND METHODS: Postmortem tissues were studied by
       a combination of histology, cell culture and molecular analyses. The
       patient had a stable CD4 count of 10 x 10(6)/I during the 12 months
       preceding death. A 540 base-pair fragment of the LTR including U3/R/U5
       was amplified using polymerase chain reaction on proviral DNA from the
       five postmortem tissues and peripheral blood mononuclear cells obtained
       2 months prior to death. The population of viral variants was determined
       by sequencing at least five plasmid clones of the amplicons. The
       relationship between the variants present in different body sites was
       investigated using molecular phylogeny methods. RESULTS: HIV-1 was
       present in all organs analysed and correlated with the presence of
       abnormal histology. Genetic variation leading to divergence from the
       consensus sequence was more frequently present in characterized
       transcription factor binding sites within the LTR (P < 0.0001) although
       the HIV-1 LTR quasispecies in the different body sites showed similar,
       relatively low levels of divergence (intra-organ median heterogeneity
       ranging from 0.0094 to 0.017). Phylogenetic analysis showed that the
       spinal cord and dorsal root ganglion harboured an LTR population
       genetically distinct from that present in other organs and more closely
       related to a previously characterized neurotropic strain of HIV (strain
       JRcsf). CONCLUSION: The independent clustering of HIV-1 LTR variants
       present in spinal cord and dorsal root ganglion shows that HIV-1 LTR
       evolution can occur in a compartmentalized fashion. The data show that
       the LTR is an important region to analyse in sequence variation studies
       of HIV since it may play a role in nervous tissue adaptation of HIV-1
       and neuropathogenicity. Outgrowth of HIV-1 LTR variants that are most
       fit for the utilization of tissue-specific transcription factors can
       occur in the nervous tissue.
 DE    Acquired Immunodeficiency Syndrome/BLOOD/*GENETICS  Base Sequence  Case
       Report  Ganglia, Spinal/VIROLOGY  Genetic Heterogeneity  Human  *HIV
       Long Terminal Repeat  HIV-1/CLASSIFICATION/*GENETICS  Lung/VIROLOGY
       Lymph Nodes/VIROLOGY  Male  Molecular Sequence Data  Phylogeny
       Polymerase Chain Reaction  Sequence Alignment  Spinal Cord/VIROLOGY
       Support, Non-U.S. Gov't  JOURNAL ARTICLE

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

