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Organ-specific differences in populations of HIV-1 env sequence variants in vivo.
Donaldson Y; Rebus S; Bell J; Brown AL; Simmonds P; Department of
November 30, 1993
Int Conf AIDS. 1993 Jun 6-11;9(1):178 (abstract no. PO-A14-0264). Unique

The populations of HIV sequence variants in (1) different organs and (2) different regions of the same organ were compared to explore whether specific local populations reflect differences in cell tropism or arise as a consequence of the dynamics of HIV spread throughout the body. HIV proviral DNA was extracted from various organs (colon, liver, lung, brain, spinal cord, lymph node and spleen) taken at post mortem from patients who died of AIDS or asymptomatic individuals (CDC II) who died for unrelated reasons. Proviral DNA was quantified using limiting dilution and nested PCR with primers in the gag region (Simmonds et al., J Virol; 64:864). RNA was extracted from plasma, reverse transcribed and amplified as previously described (Zhang et al., AIDS; 5:675). Viral populations were examined by length and sequence analysis of hypervariable regions of the env gene Simmonds et al., J Virol; 64: 5840). The extent of infection varied widely between patients and correlated with disease progression. Distribution of HIV in different organs was also found to be variable between patients. To investigate whether populations differed because of adaptation, DNA was extracted from different regions of the same organ. The finding of distinct populations at different sites within an organ suggests a substantial random component in the distribution of env sequences in vivo. However, this does not rule out an association of specific V3 sequences with lymphoid and non-lymphoid tissue. Indeed, we have obtained some evidence that brain, lung and colon are infected with a restricted range of V3 sequences closely corresponding to those associated with macrophage tropism.

*Genes, env *HIV Infections/MICROBIOLOGY *HIV-1/GENETICS

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