Phenotype associated env gene variation among 8 related HIV-1 clones: evidence for in vivo recombination and determinants of cytotropism outside the V3 domain.

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Phenotype associated env gene variation among 8 related HIV-1 clones: evidence for in vivo recombination and determinants of cytotropism outside the V3 domain.

Int Conf AIDS. 1992 Jul 19-24;8(1):Mo20 (abstract no. MoA 0075). Unique Identifier : AIDSLINE ICA8/92400031
Groenink M; Andeweg AC; van der Jagt RC; Schuitemaker H; Bosch ML; Huisman JG; Tersmette M; Centr. Lab. Netherlands Red Cross Blood Transf. Serv., Amsterdam.

Abstract: OBJECTIVES: To genetically compare phenotypically heterogeneous HIV-1 variants and to analyze regions of the HIV-1 env gene previously identified as determinants of biological properties. METHODS: Eight phenotypically heterogeneous HIV-1 clones, recovered directly from a single patient peripheral blood mononuclear cells under limiting dilution conditions, were compared for the nucleotide sequences of their env genes. In addition, the accessory gene sequences were obtained for four of these clones. RESULTS: Four clones with intermediate phenotypes were the product of genetic recombination events. In contrast to the accessory genes, all 8 HIV-1 clones demonstrated extensive phenotype-associated sequence variation dispersed non-randomly over the env gene. Sequence variation associated with syncytium inducing (SI) capacity and tropism for the MT2 T-cell line was concentrated in the C1-V4 region of the gp120 glycoprotein. In contrast, sequence variation associated with tropism for the H9 and Sup T1 T-cell lines was completely limited to the gp120-V5 region and the gp41 glycoprotein. The fusion domain, and amino acids involved in gp120-CD4 and gp120-gp41 interaction and their directly surrounding residues were completely conserved. The SI clones, which differed in their tropism for primary monocytes and T-cell lines possessed identical V3 sequences. CONCLUSION: Three clones most likely resulted from genetic recombination events in vivo, indicating that this phenomenon may account for the emergence of proviruses with novel phenotypic properties during the course of the HIV-1 infection. Variation among most accessory genes was limited. The finding of identical V3 sequences in clones differing in tropism for primary monocytes and T-cell lines demonstrated the existence of determinants of tropism outside the env V3 region, most probably located within the gp120-V5 region and the gp41 molecule.

Keywords: Antigenic Variation/GENETICS Cells, Cultured *Genes, env Human HIV Envelope Protein gp120/*GENETICS/PHYSIOLOGY HIV Envelope Protein gp41/*GENETICS/PHYSIOLOGY HIV Infections/MICROBIOLOGY HIV-1/*GENETICS/ISOLATION & PURIF/PHYSIOLOGY Leukocytes, Mononuclear/MICROBIOLOGY Phenotype Recombination, Genetic T-Lymphocytes/MICROBIOLOGY ABSTRACT
921230
M92C5316

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