PMID- 36525463 OWN - NLM STAT- MEDLINE DCOM- 20230103 LR - 20230208 IS - 1553-7374 (Electronic) IS - 1553-7366 (Print) IS - 1553-7366 (Linking) VI - 18 IP - 12 DP - 2022 Dec TI - Adaptation to HLA-associated immune pressure over the course of HIV infection and in circulating HIV-1 strains. PG - e1010965 LID - 10.1371/journal.ppat.1010965 [doi] LID - e1010965 AB - Adaptation to human leukocyte antigen (HLA)-associated immune pressure represents a major driver of human immunodeficiency virus (HIV) evolution at both the individual and population level. To date, there has been limited exploration of the impact of the initial cellular immune response in driving viral adaptation, the dynamics of these changes during infection and their effect on circulating transmitting viruses at the population level. Capturing detailed virological and immunological data from acute and early HIV infection is challenging as this commonly precedes the diagnosis of HIV infection, potentially by many years. In addition, rapid initiation of antiretroviral treatment following a diagnosis is the standard of care, and central to global efforts towards HIV elimination. Yet, acute untreated infection is the critical period in which the diversity of proviral reservoirs is first established within individuals, and associated with greater risk of onward transmissions in a population. Characterizing the viral adaptations evident in the earliest phases of infection, coinciding with the initial cellular immune responses is therefore relevant to understanding which changes are of greatest impact to HIV evolution at the population level. In this study, we utilized three separate cohorts to examine the initial CD8+ T cell immune response to HIV (cross-sectional acute infection cohort), track HIV evolution in response to CD8+ T cell-mediated immunity over time (longitudinal chronic infection cohort) and translate the impact of HLA-driven HIV evolution to the population level (cross-sectional HIV sequence data spanning 30 years). Using next generation viral sequencing and enzyme-linked immunospot interferon-gamma recall responses to peptides representing HLA class I-specific HIV T cell targets, we observed that CD8+ T cell responses can select viral adaptations prior to full antibody seroconversion. Using the longitudinal cohort, we uncover that viral adaptations have the propensity to be retained over time in a non-selective immune environment, which reflects the increasing proportion of pre-adapted HIV strains within the Western Australian population over an approximate 30-year period. CI - Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. FAU - Alves, Eric AU - Alves E AUID- ORCID: 0000-0002-6072-708X AD - School of Human Sciences, The University of Western Australia, Perth, Western Australia, Australia. FAU - Al-Kaabi, Marwah AU - Al-Kaabi M AD - School of Human Sciences, The University of Western Australia, Perth, Western Australia, Australia. FAU - Keane, Niamh M AU - Keane NM AD - Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia, Australia. FAU - Leary, Shay AU - Leary S AD - Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia, Australia. FAU - Almeida, Coral-Ann M AU - Almeida CM AD - Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia, Australia. FAU - Deshpande, Pooja AU - Deshpande P AD - School of Human Sciences, The University of Western Australia, Perth, Western Australia, Australia. AD - Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia, Australia. FAU - Currenti, Jennifer AU - Currenti J AD - School of Human Sciences, The University of Western Australia, Perth, Western Australia, Australia. FAU - Chopra, Abha AU - Chopra A AD - Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia, Australia. FAU - Smith, Rita AU - Smith R AD - Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America. FAU - Castley, Alison AU - Castley A AD - Department of Clinical Immunology, Royal Perth Hospital, Perth, Western Australia, Australia. FAU - Mallal, Simon AU - Mallal S AD - Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia, Australia. AD - Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America. FAU - Kalams, Spyros A AU - Kalams SA AD - Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America. FAU - Gaudieri, Silvana AU - Gaudieri S AUID- ORCID: 0000-0001-6873-0198 AD - School of Human Sciences, The University of Western Australia, Perth, Western Australia, Australia. AD - Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia, Australia. AD - Division of Infectious Diseases, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, United States of America. FAU - John, Mina AU - John M AD - Institute for Immunology and Infectious Diseases, Murdoch University, Perth, Western Australia, Australia. AD - Department of Clinical Immunology, Royal Perth Hospital, Perth, Western Australia, Australia. LA - eng GR - P30 AI110527/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20221216 PL - United States TA - PLoS Pathog JT - PLoS pathogens JID - 101238921 RN - 0 (Histocompatibility Antigens Class I) RN - 0 (HLA Antigens) RN - 0 (Histocompatibility Antigens Class II) SB - IM MH - Humans MH - *HIV Infections MH - *HIV-1 MH - Cross-Sectional Studies MH - Australia MH - Histocompatibility Antigens Class I MH - HLA Antigens MH - Histocompatibility Antigens Class II MH - CD8-Positive T-Lymphocytes PMC - PMC9803285 COIS- The authors have declared that no competing interests exist. EDAT- 2022/12/17 06:00 MHDA- 2023/01/04 06:00 PMCR- 2022/12/16 CRDT- 2022/12/16 13:42 PHST- 2022/07/27 00:00 [received] PHST- 2022/11/01 00:00 [accepted] PHST- 2022/12/30 00:00 [revised] PHST- 2022/12/17 06:00 [pubmed] PHST- 2023/01/04 06:00 [medline] PHST- 2022/12/16 13:42 [entrez] PHST- 2022/12/16 00:00 [pmc-release] AID - PPATHOGENS-D-22-01304 [pii] AID - 10.1371/journal.ppat.1010965 [doi] PST - epublish SO - PLoS Pathog. 2022 Dec 16;18(12):e1010965. doi: 10.1371/journal.ppat.1010965. eCollection 2022 Dec.