Analysis of neutralizing and enhancing antibodies to human immunodeficiency virus type 1 primary isolates in plasma of individuals infected with env genetic subtype B and E viruses in Thailand

Abstract

Twenty-seven HIV-1 isolates were obtained from 51 asymptomatic HIV-l-infected pregnant women or intravenous drug users (IDUs) in Bangkok. Using heteroduplex mobility assay (HMA), it was found that the majority of the HIV-1 isolates (9 out of 11) from pregnant women belonged to genetic subtype E, whereas most of the subtype B HIV-1 isolates (15 out of 16) were isolated from IDUs. The HIV-1 isolates were tested for their susceptibility to neutralization or antibody-dependent enhancement with homologous and heterologous plasma of the two different genetic subtypes, B and E. Overall, HIV-1 neutralizing activity could be found in 37.3% of virus/plasma pairs for both subtypes B and E. No significant correlation could be identified between the two genetic subtypes (B and E) and their susceptibility to neutralization. Subtype B plasma demonstrated frequent cross-neutralization of subtype E viruses in 38.5% of virus/plasma pairs, whereas cross-neutralization activity of subtype E specific plasma samples was more limited and could cross-neutralize subtype B viruses only in 15.8% of cases. Some of the viral strains independently of their genetic subtypes were more susceptible to neutralization by plasma specific for both subtype E or subtype B, suggesting that this phenomenon is related to the proper biological properties of a viral strain. Antibody-dependent enhancement of HIV-1 strains could be detected in 12/83 (14.5%) virus-plasma pairs irrespective of genetic subtypes. Similar to neutralization results, the HIV-1 enhancing activity of plasma was mostly isolate-specific. The HIV isolates that were susceptible to neutralization were not enhanced by any plasma. On the other hand, the HIV isolates that were enhanced by plasma were resistant to neutralization in most cases, Such a dissociation between susceptibility to neutralization or enhancement may be indicative of the existence of discrete epitopes determining the two distinct viral properties.