Limited neutralizing antibody specificities drive neutralization escape in early HIV-1 subtype C infection
Journal Article
2009
Permanent link to this Item
Authors
Journal Title
PLoS One
Link to Journal
Journal ISSN
Volume Title
Publisher
Public Library of Science
Publisher
University of Cape Town
Faculty
Series
Abstract
Author Summary Most HIV-1 infected individuals develop neutralizing antibodies against their own virus, termed an autologous neutralizing response. It is known that this response exerts pressure on the envelope of HIV, the target of such antibodies, resulting in neutralization escape. Here we have identified the targets of these antibodies and the precise genetic basis of neutralization escape in 4 individuals infected with HIV-1 subtype C. We show that V1V2 is commonly involved in escape, and that the C3 region is also a target in some cases. The latter observation confirms this region is exposed in subtype C, unlike subtype B. We show that neutralization escape is conferred by a few amino acid mutations, some of which are outside the antibody target site. Moreover, escape from these limited specificities even within a single individual occurs via a variety of different pathways involving substitutions, indels and glycan shifts. The finding in 2 individuals that an anti-C3 response developed first, followed by an anti-V1V2 response, suggests there may be specific regions of envelope particularly vulnerable to antibody neutralization. Overall, we propose a mechanistic explanation for how HIV-1 epitopes drive sequential waves of neutralization escape in early subtype C infection.
Description
Keywords
Reference:
Moore, P. L., Ranchobe, N., Lambson, B. E., Gray, E. S., Cave, E., Abrahams, M. R., ... & Morris, L. (2009). Limited neutralizing antibody specificities drive neutralization escape in early HIV-1 subtype C infection. PLoS Pathog, 5(9), e1000598. doi:10.1371/journal.ppat.1000598