The genetic interaction between HIV and the antibody repertoire

Abstract

The interaction between human immunodeficiency virus (HIV) and the antibody repertoire (AbR) during chronic infection can provide important information for HIV vaccine research, yet has not been well-characterized on a systems level. We deeply sequenced the HIV population and the AbR of ten HIV-infected, antiretroviral (ART)-naïve individuals, each with 10-20 longitudinal samples spanning 4-14 years. Our unbiased sequencing approach identified partitions of AbRs showing evidence of interaction with autologous HIV populations. We show that these HIV-associated partitions are enriched for the V gene segments of known HIV broadly neutralizing antibodies (bnAbs), indicating that the HIV-responding component of the AbR can be identified via time-series genetic data. Despite this evidence for larger-scale AbR/HIV interactions at the sub-population level, we found little to no evidence for coevolution. This suggests that coevolution is either rare, or hard to detect, which has important vaccine design implications.