Intrapatient variability of the human immunodeficiency virus type 2 envelope V3 loop.
ABSTRACT Studies of HIV-2 infection have shown lower rates of sexual and perinatal transmission and a prolonged incubation period to AIDS as compared to HIV-1. To evaluate the role of genetic variation in HIV pathogenesis, we studied intrapatient variability in the V3 loop of the HIV-2 envelope gene over time in five seropositive individuals. Proviral sequences derived from uncultured PBMC DNA (n = 102) demonstrated an average sequence heterogeneity within a sample of 1.4% (0-4.1%). This was significantly lower than the V3 sequence heterogeneity observed in HIV-1, which can be as high as 6.1%. In HIV-2-seropositive healthy patients the average intrapatient nucleotide variability rate was 0.6% compared to 2.0% in patients with clinical AIDS. The lower rate of variability between HIV-2 and HIV-1 is compatible with differences in transmission and pathogenesis of these two related viruses.
Article: Autologous and heterologous neutralizing antibody responses following initial seroconversion in human immunodeficiency virus type 1-infected individuals.[show abstract] [hide abstract]
ABSTRACT: In the course of human immunodeficiency virus type 1 (HIV-1) infection, patients develop a strong and persistent immune response characterized by the production of HIV-specific antibodies. The aim of our study was to analyze the appearance of autologous and heterologous neutralizing antibodies in the sera of HIV-infected individuals. For this purpose, primary strains have been isolated from 18 HIV-1-infected subjects prior to seroconversion (in one case) or within 1 to 8 months after seroconversion. Sera, collected at the same time as the virus was isolated and at various times after isolation, have been analyzed for their ability to neutralize the autologous primary strains isolated early after infection, heterologous primary isolates, and cell-line adapted strains. Our neutralization assay, which combines serial dilutions of virus and serial dilutions of sera, is based on the determination of the serum dilution at which a fixed reduction in virus titer (90%) occurs. We have shown that (i) we could not detect autologous neutralizing antibodies in sera collected at the same time as we isolated viruses; (ii) we detected neutralizing antibodies against the autologous strains about 1 year after seroconversion, occasionally after 8 months, but sera were not always available to exclude the presence of neutralizing antibodies at earlier times; (iii) after 1 year, the neutralization response was highly specific to virus present during the early phase of HIV infection; and (iv) heterologous neutralization of primary isolates was detected later (after about 2 years). These results reveal the enormous diversity of neutralization determinants on primary isolates as well as a temporal evolution of the humoral response generating cross-reactive neutralizing antibodies.Journal of Virology 06/1997; 71(5):3734-41. · 5.40 Impact Factor