Impact of pre-adapted HIV transmission

J.M. Carlson; V.Y. Du; N. Pfeifer; A. Bansal; V.Y.F. Tan; K. Power; C.J. Brumme; A. Kreimer; C.E DeZiel; N. Fusi; M. Schaefer; M.A. Brockman; J. Gilmour; M.A. Price; W. Kilembe; R. Haubrich; M. John; S. Mallal; R. Shapiro; J. Frater; P.R. Harrigan; T. Ndung'u; S. Allen; D. Heckerman; J. Sidney; T.M. Allen; P.J.R. Goulder; Z.L. Brumme; E. Hunter; P.A. Goepfert

doi:10.1038/nm.4100

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Impact of pre-adapted HIV transmission

J.M. Carlson, V.Y. Du, N. Pfeifer, A. Bansal, V.Y.F. Tan, K. Power, C.J. Brumme, A. Kreimer, C.E DeZiel, N. Fusi, …

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

2016

DOI: https://doi.org/10.1038/nm.4100

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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.

Details

Title: Impact of pre-adapted HIV transmission
Authors/Creators: J.M. Carlson (Author/Creator) - Microsoft (United States)
V.Y. Du (Author/Creator) - University of Alabama at Birmingham
N. Pfeifer (Author/Creator) - Max Planck Society
A. Bansal (Author/Creator)
V.Y.F. Tan (Author/Creator) - Microsoft (United States)
K. Power (Author/Creator) - Ragon Institute of MGH, MIT and Harvard
C.J. Brumme (Author/Creator) - AIDS Vancouver
A. Kreimer (Author/Creator) - Microsoft (United States)
C.E DeZiel (Author/Creator) - Microsoft (United States)
N. Fusi (Author/Creator) - Microsoft (United States)
M. Schaefer (Author/Creator) - Yerkes National Primate Research Center
M.A. Brockman (Author/Creator) - AIDS Vancouver
J. Gilmour (Author/Creator) - Imperial College London
M.A. Price (Author/Creator) - University of California, San Francisco
W. Kilembe (Author/Creator) - Rwanda Zambia HIV Research Group
R. Haubrich (Author/Creator) - Gilead Sciences (United States)
M. John (Author/Creator) - Royal Perth Hospital
S. Mallal (Author/Creator) - Vanderbilt University
R. Shapiro (Author/Creator) - Harvard University
J. Frater (Author/Creator) - University of Oxford
P.R. Harrigan (Author/Creator) - University of British Columbia
T. Ndung'u (Author/Creator) - Max Planck Society
S. Allen (Author/Creator) - Rwanda Zambia HIV Research Group
D. Heckerman (Author/Creator) - Microsoft (Canada)
J. Sidney (Author/Creator) - La Jolla Institute for Immunology
T.M. Allen (Author/Creator) - Ragon Institute of MGH, MIT and Harvard
P.J.R. Goulder (Author/Creator) - University of Oxford
Z.L. Brumme (Author/Creator) - AIDS Vancouver
E. Hunter (Author/Creator) - Rwanda Zambia HIV Research Group
P.A. Goepfert (Author/Creator) - University of Alabama at Birmingham
Publication Details: Nature Medicine, Vol.22(6), pp.606-613
Publisher: Nature Publishing Group
Identifiers: 991005542570407891
Copyright: © 2016 Macmillan Publishers Limited
Murdoch Affiliation: Institute for Immunology and Infectious Diseases
Language: English
Resource Type: Journal article

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Collaboration types: Industry collaboration; Domestic collaboration; International collaboration
Citation topics: 1 Clinical & Life Sciences; 1.66 HIV; 1.66.46 HIV Pathogenesis
Web Of Science research areas: Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental
ESI research areas: Molecular Biology & Genetics