Impact of pre-adapted HIV transmission

Jonathan M Carlson; Victor Y Du; Nico Pfeifer; Anju Bansal; Vincent Y F Tan; Karen Power; Chanson J Brumme; Anat Kreimer; Charles E DeZiel; Nicolo Fusi; Malinda Schaefer; Mark A Brockman; Jill Gilmour; Matt A Price; William Kilembe; Richard Haubrich; Mina John; Simon Mallal; Roger Shapiro; John Frater; P Richard Harrigan; Thumbi Ndung'u; Susan Allen; David Heckerman; John Sidney; Todd M Allen; Philip J R Goulder; Zabrina L Brumme; Eric Hunter; Paul A Goepfert

doi:10.1038/nm.4100

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Journal article

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Impact of pre-adapted HIV transmission

Jonathan M Carlson, Victor Y Du, Nico Pfeifer, Anju Bansal, Vincent Y F Tan, Karen Power, Chanson J Brumme, Anat Kreimer, Charles E DeZiel, Nicolo Fusi, …

Nature medicine, Vol.22(6), pp.606-613

06/01/2016

DOI: 10.1038/nm.4100

PMCID: PMC4899163

PMID: 27183217

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http://nrs.harvard.edu/urn-3:HUL.InstRepos:29626042View

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Abstract

Human leukocyte antigen class I (HLA)-restricted CD8(+) T lymphocyte (CTL) responses are crucial to HIV-1 control. Although HIV can evade these responses, the longer-term impact of viral escape mutants remains unclear, as these variants can also reduce intrinsic viral fitness. To address this, we here developed a metric to determine the degree of HIV adaptation to an HLA profile. We demonstrate that transmission of viruses that are pre-adapted to the HLA molecules expressed in the recipient is associated with impaired immunogenicity, elevated viral load and accelerated CD4(+) T cell decline. Furthermore, the extent of pre-adaptation among circulating viruses explains much of the variation in outcomes attributed to the expression of certain HLA alleles. Thus, viral pre-adaptation exploits 'holes' in the immune response. Accounting for these holes may be key for vaccine strategies seeking to elicit functional responses from viral variants, and to HIV cure strategies that require broad CTL responses to achieve successful eradication of HIV reservoirs.

Adaptation, Physiological - immunology

Africa, Southern

AIDS Vaccines - immunology

British Columbia

CD4 Lymphocyte Count

CD8-Positive T-Lymphocytes - immunology

Cohort Studies

Evolution, Molecular

Histocompatibility Antigens Class I - immunology

HIV Infections - immunology

HIV Infections - transmission

HIV-1 - genetics

HIV-1 - immunology

Humans

Immune Evasion - genetics

Immune Evasion - immunology

Immunity, Cellular - immunology

Linear Models

Models, Immunological

Proportional Hazards Models

Receptors, Antigen, T-Cell - immunology

Viral Load

Virus Replication - genetics

Details

Title: Subtitle: Impact of pre-adapted HIV transmission
Creators: Jonathan M Carlson - Microsoft (United States)
Victor Y Du - University of Alabama at Birmingham
Nico Pfeifer - National University of Singapore
Anju Bansal - University of Alabama at Birmingham
Vincent Y F Tan - Max Planck Institute for Informatics
Karen Power - Ragon Institute of MGH, MIT and Harvard
Chanson J Brumme - AIDS Vancouver
Anat Kreimer - Max Planck Institute for Informatics
Charles E DeZiel - Microsoft (United States)
Nicolo Fusi - Microsoft (United States)
Malinda Schaefer - Emory University
Mark A Brockman - Simon Fraser University
Jill Gilmour - Imperial College London
Matt A Price - University of California, San Francisco
William Kilembe - Rwanda Zambia HIV Research Group
Richard Haubrich - Gilead Sciences (United States)
Mina John - Royal Perth Hospital
Simon Mallal - Vanderbilt University
Roger Shapiro - Harvard University
John Frater - Murdoch University
P Richard Harrigan - AIDS Vancouver
Thumbi Ndung'u - Max Planck Institute for Infection Biology
Susan Allen - Emory University
David Heckerman - Microsoft (United States)
John Sidney - La Jolla Institute for Immunology
Todd M Allen - Ragon Institute of MGH, MIT and Harvard
Philip J R Goulder - University of Oxford
Zabrina L Brumme - Simon Fraser University
Eric Hunter - Emory University
Paul A Goepfert - University of Alabama at Birmingham
Resource Type: Journal article
Publication Details: Nature medicine, Vol.22(6), pp.606-613
DOI: 10.1038/nm.4100
PMID: 27183217
PMCID: PMC4899163
NLM abbreviation: Nat Med
ISSN: 1078-8956
eISSN: 1546-170X
Grant note: UM1 AI068614 / NIAID NIH HHS P30 AI050409 / NIAID NIH HHS Wellcome Trust Howard Hughes Medical Institute U01 AI068636 / NIAID NIH HHS UM1 AI068635 / NIAID NIH HHS P30 AI027767 / NIAID NIH HHS P30 AI110527 / NIAID NIH HHS R01 AI046995 / NIAID NIH HHS U01 AI066454 / NIAID NIH HHS R37 AI051231 / NIAID NIH HHS R01 AI064060 / NIAID NIH HHS MR/L006588/1 / Medical Research Council WT104748MA / Wellcome Trust P01 AI074415 / NIAID NIH HHS R01 AI071906 / NIAID NIH HHS P51 OD011132 / NIH HHS UM1 AI068634 / NIAID NIH HHS R56 AI098551 / NIAID NIH HHS R01 AI112566 / NIAID NIH HHS
Language: English
Date published: 06/01/2016
Academic Unit: Obstetrics and Gynecology
Record Identifier: 9984697042902771

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