Characteristics of the env Genes of HIV Type 1 Quasispecies in Long-Term Nonprogressors With Broadly Neutralizing Antibodies

Abstract

Primary isolates of different subtypes of HIV-1 can be neutralized in vitro by the broadly neutralizing antibodies (NAbs) found in the sera of a small number of HIV-1-infected patients. This broad response is most frequent in long-term nonprogressors (LTNPs). We investigated whether the presence of NAbs in the sera of some LTNPs was associated with particular properties of the envelope glycoproteins of the variants found in these patients. Toward that aim, 147 env gene fragments (encoding almost the entire gp120) amplified from the proviral DNA of 5 LTNPs who developed broadly NAbs (NAb+) and of 4 LTNPs who did not develop such broadly NAbs (NAb-) were cloned, sequenced, and compared. We found that the development of broadly NAbs was associated with high viral loads, greater diversity in the gp120 of the viruses infecting these patients, and longer V1 sequences and additional N-gly sites in V1. In addition, a higher proportion of defective clones was found among the env genes of NAb- patients (25% to 93%)-particularly those with lower viral loads and low levels of env diversity-than among those of NAb+ patients (7% to 19%).