Low or no antibody responses to human immunodeficiency virus type 1 Nef ininfected carriers with subtype E, in contrast to subtype B that showed antibodies preferentially recognizing subtype-specific Nef epitopes

The viral accessory gene product Nef has been shown to play an important ro le in human immunodeficiency virus type 1 (HIV-1)-induced pathogenesis. Onl y little information is available regarding the differences in the host imm une responses against Nef protein and its function in vivo among different subtypes of HIV-1. In the present study, we showed marked differences in th e immune responses to Nef protein between subtypes B and E. The amino acid sequence in subtype E Nef showed 72% homology with that in subtype B. Most murine monoclonal antibodies obtained by immunization with subtype B or E N ef protein showed cross-reactivity with both Nef proteins (80 and 67%, resp ectively). Next, we focused on the immune responses among infected Japanese and Thai individuals. Subtyping of the individuals into B and E was carrie d out by enzyme-linked immunosorbent assay (ELISA) using synthetic peptides corresponding to the V3 loop representing the principal neutralizing domai n. Most of the sera from these individuals reacted strongly with Gag p24 pr oteins derived from subtypes B and E at similar levels. However, the: immun e responses among these individuals to Nef protein were markedly different. Some subtype B-infected Japanese and Thai individuals (40 and 35%, respect ively) showed higher levels of anti-Nef antibodies, although these antibodi es preferentially recognized epitopes specific to subtype B. On the other h and, most of the subtype E-infected Japanese and Thai individuals showed lo w or no antibody responses to Nef proteins. Thus, immune responses to Nef w ere markedly different between subtypes B- and E-infected carriers, suggest ing different function(s) for Nef in AIDS pathogenesis. Further, vaccine de sign must take into account the different subtypes of HIV-1, (C) 2001 Elsev ier Science Ltd. All rights reserved.