GENOMIC VARIATION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) - MOLECULAR ANALYSES OF HIV-1 IN SEQUENTIAL BLOOD-SAMPLES AND VARIOUS ORGANS OBTAINED AT AUTOPSY

Length polymorphisms and partial nucleotide sequences were determined for the hypervariable regions, V1 to V5, of the human immunodeficiency virus type 1 (HIV-1) env gene obtained from proviral DNA of sequentia l peripheral blood samples, from viral RNA in plasma, and from provira l DNA obtained from different organs of individuals at autopsy. The le ngths of several env regions of HIV-I proviral DNA differed markedly w hen obtained from different organs of an individual. Nucleotide sequen ces of the hypervariable V3 region of HIV-1 obtained from different or gans of one patient demonstrated distinct viral variants. Most provira l DNA sequences found in organs were also present in viral RNA obtaine d from plasma. The majority of HIV-1 V3 variants present in the lymph tissue could be found in the plasma viral population obtained at autop sy and in the sequential blood samples obtained before death, but were absent from the cardiac blood provirus population obtained at autopsy . However, sequence variants found in the brain proviral DNA were not detected in either plasma or the sequential blood samples. Sequence di fferences were observed at the apex of the V3 loop between HIV-1 varia nts present in sequential blood samples and in blood lymphocytes and n ervous tissue, lymph tissue and plasma obtained post-mortem. The poten tial effect of lymph tissue on the long-term persistence of different viral variants is discussed. Virus obtained from the two sequential bl ood samples produced syncytia in primary cultures and was easily trans mitted to the continuous JM cell line. Consensus (majority) V3 loop se quences determined for the adapted viruses demonstrated that some, but not all, sequences were represented within the in vivo viral populati on.