AEGiS-11IAC: In vivo recombination between two HIV-1 strains from different clades following superinfection of chimpanzees.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

In vivo recombination between two HIV-1 strains from different clades following superinfection of chimpanzees.

Int Conf AIDS 1996 Jul 7-12; 11:228 (abstract no. Tu.A.510)
Fultz PN, Wei Q, Yue L, Barre-Sinoussi F, Girard M; University of Alabama at Birmingham, Birmingham, AL, USA.

OBJECTIVE: To determine whether recombination between two HIV-1 strains from different clades occurs in vivo after superinfection of chimpanzees.

METHODS: Chimpanzees infected for more than 1 year with HIV-1LAI(IIIB) were inoculated IV with a subtype (clade) E strain, CAR/E4002. Proviral DNA was isolated from PBMC and lymph node biopsies at different times after inoculation. Heteroduplex mobility assays (HMA) were used to screen multiple clones generated from PCR amplification products of the entire env gene or a fragment spanning the V2 to V5 region of env. Nucleotide sequences of clones that exhibited unusual mobility, patterns were obtained and compared with those of the two inoculated strains.

RESULTS: Chimpanzees infected with the clade B HIV-1 strain LAI(IIIB) for up to 32 months readily became infected with the clade E strain CAR/E4002, as shown by increased antibody titers to HIV-1 and isolation of the second virus from PBMC 2 weeks after inoculation. HMA of at least 20 clones from PBMC and lymph node cells revealed changes in the relative proportion of the two HIV-1 strains over time and the presence of possible recombinant viruses. In DNA isolated from lymph node tissue obtained 24 months after infection with the second virus, two different recombinants were identified in multiple independent PCR assays. These recombinants were confirmed by DNA sequence analysis.

CONCLUSIONS: Infection with and recombination between two diverse strains of HIV-1 can occur in vivo even though the second strain establishes infection after the first strain. Although the clade E HIV-1 predominated in PBMC initially, within 6 weeks after inoculation, it declined and became the minor viral species suggesting immune-mediated control. These results indicate there is ongoing active replication of HIV-1 in clinically asymptomatic chimpanzees, as in humans.

Keywords: AEGIS, HIV-1, Pan troglodytes, Superinfection, HIV Antibodies, Recombination, Genetic, Genes, env, HIV Infections, HIV Antigens, HIV Envelope Protein gp120, HIV, HIV Core Protein p24, Receptors, HIV, Polymerase Chain Reaction, Animal, Human, genetics, ICA11

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TuA510