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

Autoři: Jennifer Currenti aff001;  Abha Chopra aff002;  Mina John aff002;  Shay Leary aff002;  Elizabeth McKinnon aff002;  Eric Alves aff001;  Mark Pilkinton aff004;  Rita Smith aff004;  Louise Barnett aff004;  Wyatt J. McDonnell aff004;  Michaela Lucas aff005;  Francine Noel aff006;  Simon Mallal aff002;  Joseph A. Conrad aff007;  Spyros Kalams aff004;  Silvana Gaudieri aff001
Působiště autorů: School of Human Sciences, University of Western Australia, Crawley, Western Australia, Australia aff001;  Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia, Australia aff002;  Department of Clinical Immunology, Royal Perth Hospital, Perth, Western Australia, Australia aff003;  Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America aff004;  School of Medicine, University of Western Australia, Crawley, Western Australia, Australia aff005;  GHESKIO Centre, Port-au-prince, Haiti aff006;  Department of Chemistry, Vanderbilt University, Nashville, Tennessee, United States of America aff007
Vyšlo v časopise: Deep sequence analysis of HIV adaptation following vertical transmission reveals the impact of immune pressure on the evolution of HIV. PLoS Pathog 15(12): e32767. doi:10.1371/journal.ppat.1008177
Kategorie: Research Article
doi: 10.1371/journal.ppat.1008177


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

Klíčová slova:

Cell cycle and cell division – Evolutionary adaptation – Immune response – Polymerase chain reaction – T cells – Viral load – Viral replication


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