AEGiS-11IAC: Evidences for an immune selection pressure on the first hypervariable region of HIV-1 and HIV-2 ENV genes in vivo.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Evidences for an immune selection pressure on the first hypervariable region of HIV-1 and HIV-2 ENV genes in vivo.

Int Conf AIDS 1996 Jul 7-12; 11:228 (abstract no. Tu.A.512)
Lu W, Andrieu JM; Laboratoire d'Immunologie des Tumeurs, Paris, France. Fax: 33 (1) 4439-6465.

OBJECTIVE: To depict the relationship between the variation in length of the first hypervariable region (V1) of HIV env gene and isolate-specific neutralizating antibody response along the course of the infection. Methods and

RESULTS: A viro-immunological study was conducted on four HIV-1 infected individuals and one HIV-2 infected subject from less than 10 weeks to 3-6 years after their seroconversion. Polymerase chain reaction (PCR) demonstrated that near the time of serovonversion a single band of the V1 fragment was observed in the serum-derived HIV RNA of all individuals; its length was however different in each patient. It was intriguing that one HIV-1 seroconverter who failed to mount neutralizing antibodies and progressed to AIDS rapidly (less than 2 years) exhibited a constant single V1 band over time, although HIV-specific cytotoxic T lymphocytes (CTLs) activity was steadily detected during the course of the infection. In the remaining three HIV-1 infected patients who developed isolate-specific neutralizing response shortly after seroconversion and remained asymptomatic for 4-6 years, their V1 genes evolved rapidly from a single band to multiple bands. Fluctuation in the length of multiple V1 bands was associated with temporal change in sensitivity of the viral isolates to neutralization by autologous sera. The cessation of this V1-length fluctuation was associated with emergence of neutralization-resistant variants that preceded the accelerated CD4+ T-cell depletion and disease progression. In a 6-year follow-up of one seroconverter with asymptomatic HIV-2 infection, fluctuation in the length of a single V1 band and dynamic isolate-specific neutralizing antibody response were observed in parallel. In contrast, when the HIV isolates taken from PBMC of all five patients at a time close to their seroconversion were cultured over 1 year (greater than 10 passages) in donor PBMC (i.e. without the selection pressure of the immune system), their V1 band remained constantly unchanged.

CONCLUSIONS: These findings denote that neutralizing antibody response to HIV constitutes one of the main selective forces to drive viral diversity in vivo and that absence or loss of this selection presure predict the virus spread and disease progression.

Keywords: AEGIS, HIV-2, HIV-1, Genes, env, Complementarity Determining Regions, HIV Infections, Acquired Immunodeficiency Syndrome, Selection (Genetics), Variation (Genetics), Polymerase Chain Reaction, Human, genetics, ICA11

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TuA512