Deep sequence analysis of HIV adaptation following vertical transmission reveals the 2 impact of immune pressure on the evolution of HIV

Jennifer Currenti, Abha Chopra, Mina John, Shay Leary, Bethy McKinnon, Eric Alves, Mark A. Pilkinton, Rita Smith, L. Barnett, Wyatt J. McDonnell, Michaela Lucas, Francine Noel, Simon Mallal, Joseph A. Conrad, Spyros Kalams, Silvana Gaudieri

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Human immunodeficiency virus (HIV) can adapt to an individual’s T cell immune response via 36 genomic mutations that affect antigen recognition and impact disease outcome. These viral 37 adaptations are specific to the host’s human leucocyte antigen (HLA) alleles, as these molecules 38 determine which peptides are presented to T cells. As HLA molecules are highly polymorphic at 39 the population level, horizontal transmission events are most commonly between HLA40 mismatched donor/recipient pairs, representing new immune selection environments for the 41 transmitted virus. In this study, we utilised a deep sequencing approach to determine the HIV 42 quasispecies in 26 mother-to-child transmission pairs where the potential for founder viruses to 43 be pre-adapted is high due to the pairs being haplo-identical at HLA loci. This scenario allowed
44 the assessment of specific HIV adaptations following transmission in either a non-selective 45 immune environment, due to recipient HLA mismatched to original selecting HLA, or a selective 46 immune environment, mediated by matched donor/recipient HLA. We show that the pattern of 47 reversion or fixation of HIV adaptations following transmission provides insight into the 48 replicative cost, and likely compensatory networks, associated with specific adaptations in vivo. 49 Furthermore, although transmitted viruses were commonly heavily pre-adapted to the child’s 50 HLA genotype, we found evidence of de novo post-transmission adaptation, representing new 51 epitopes targeted by the child’s T cell response. High-resolution analysis of HIV adaptation is 52 relevant when considering vaccine and cure strategies for individuals exposed to adapted viruses 53 via transmission or reactivated from reservoirs
Original languageEnglish
Article numbere1008177
JournalPLoS Pathogens
Volume15
Issue number12
DOIs
Publication statusPublished - 10 Dec 2019

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