Phylogenetic relationship between human immunodeficiency virus type 1 (HIV-1) long terminal repeat natural variants present in the lymph node and peripheral blood of three HIV-1-infected individuals.
PCR has been used to amplify a 540 base pair fragment of the human immunodeficiency virus type 1 (HIV-1) long terminal repeat region encompassing the U5/R/U3 regions from proviral HIV DNA that was present in the lymph nodes and peripheral blood mononuclear cells of three HIV-infected individuals. The resulting PCR products were cloned and the DNA sequence of multiple clones from each reaction was determined to enable the distribution and phylogenetic relationship between the variants in each body site to be assessed. The results of bootstrapped parsimony phylogenetic analyses showed that a distinct polarization was evident between peripheral blood and lymph node variants in the patient who possessed a histologically intact lymph node. In contrast, similar analyses conducted on samples from two patients with extensive lymph node disruption showed similar variants in lymph node and peripheral blood. In the patient with an intact lymph node, lymph node variants were significantly more heterogeneous than those present in blood samples taken either simultaneously or 11 months later. No differences in heterogeneity between lymph node and peripheral blood were observed in patients with disrupted lymph nodes. The significance of these results for our understanding of HIV pathogenesis is discussed.
Division of Communicable Diseases, Royal Free Hospital School of Medicine, Hampstead, London, U.K.
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Ait-Khaled
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Emery
D001483:Base Sequence; D003001:Cloning, Molecular; D016384:Consensus Sequence; D004279:DNA, Viral / Q000032:analysis / Q000097:blood; D014644:Genetic Variation / Q000235:genetics*; D015658:HIV Infections / Q000382:microbiology*; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000382:microbiology; D008198:Lymph Nodes / Q000382:microbiology; D008969:Molecular Sequence Data; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D011533:Proviruses / Q000235:genetics; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA
D004279:DNA, Viral