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Impact of Pre-adapted HIV Transmission

Human Leukocyte Antigen class I (HLA) restricted CD8(+) T lymphocyte (CTL) responses are critical to HIV-1 control. Although HIV can evade these responses, the longer-term impact of viral escape mutants remains unclear, since these variants can also reduce intrinsic viral fitness. To address this qu...

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Autores principales: Carlson, Jonathan M., Du, Victor Y., Pfeifer, Nico, Bansal, Anju, Tan, Vincent Y.F., Power, Karen, Brumme, Chanson J., Kreimer, Anat, DeZiel, Charles E., Fusi, Nicolo, Schaefer, Malinda, Brockman, Mark A., Gilmour, Jill, Price, Matt A., Kilembe, William, Haubrich, Richard, John, Mina, Mallal, Simon, Shapiro, Roger, Frater, John, Harrigan, P. Richard, Ndung’u, Thumbi, Allen, Susan, Heckerman, David, Sidney, John, Allen, Todd M., Goulder, Philip J.R., Brumme, Zabrina L., Hunter, Eric, Goepfert, Paul A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899163/
https://www.ncbi.nlm.nih.gov/pubmed/27183217
http://dx.doi.org/10.1038/nm.4100
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author Carlson, Jonathan M.
Du, Victor Y.
Pfeifer, Nico
Bansal, Anju
Tan, Vincent Y.F.
Power, Karen
Brumme, Chanson J.
Kreimer, Anat
DeZiel, Charles E.
Fusi, Nicolo
Schaefer, Malinda
Brockman, Mark A.
Gilmour, Jill
Price, Matt A.
Kilembe, William
Haubrich, Richard
John, Mina
Mallal, Simon
Shapiro, Roger
Frater, John
Harrigan, P. Richard
Ndung’u, Thumbi
Allen, Susan
Heckerman, David
Sidney, John
Allen, Todd M.
Goulder, Philip J.R.
Brumme, Zabrina L.
Hunter, Eric
Goepfert, Paul A.
author_facet Carlson, Jonathan M.
Du, Victor Y.
Pfeifer, Nico
Bansal, Anju
Tan, Vincent Y.F.
Power, Karen
Brumme, Chanson J.
Kreimer, Anat
DeZiel, Charles E.
Fusi, Nicolo
Schaefer, Malinda
Brockman, Mark A.
Gilmour, Jill
Price, Matt A.
Kilembe, William
Haubrich, Richard
John, Mina
Mallal, Simon
Shapiro, Roger
Frater, John
Harrigan, P. Richard
Ndung’u, Thumbi
Allen, Susan
Heckerman, David
Sidney, John
Allen, Todd M.
Goulder, Philip J.R.
Brumme, Zabrina L.
Hunter, Eric
Goepfert, Paul A.
author_sort Carlson, Jonathan M.
collection PubMed
description Human Leukocyte Antigen class I (HLA) restricted CD8(+) T lymphocyte (CTL) responses are critical to HIV-1 control. Although HIV can evade these responses, the longer-term impact of viral escape mutants remains unclear, since these variants can also reduce intrinsic viral fitness. To address this question, we here develop a metric to determine the degree of HIV adaptation to an HLA profile. We demonstrate that transmission of viruses pre-adapted to the HLA molecules expressed in the recipient is associated with impaired immunogenicity, elevated viral load and accelerated CD4 decline. Furthermore, the extent of pre-adaptation among circulating viruses explains much of the variation in outcomes attributed to expression of certain HLA alleles. Thus, viral pre-adaptation exploits “holes” in the immune response. Accounting for these holes may be critical for vaccine strategies seeking to elicit functional responses from viral variants, and to HIV cure strategies requiring broad CTL responses to achieve successful eradication of HIV reservoirs.
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spelling pubmed-48991632016-11-16 Impact of Pre-adapted HIV Transmission Carlson, Jonathan M. Du, Victor Y. Pfeifer, Nico Bansal, Anju Tan, Vincent Y.F. Power, Karen Brumme, Chanson J. Kreimer, Anat DeZiel, Charles E. Fusi, Nicolo Schaefer, Malinda Brockman, Mark A. Gilmour, Jill Price, Matt A. Kilembe, William Haubrich, Richard John, Mina Mallal, Simon Shapiro, Roger Frater, John Harrigan, P. Richard Ndung’u, Thumbi Allen, Susan Heckerman, David Sidney, John Allen, Todd M. Goulder, Philip J.R. Brumme, Zabrina L. Hunter, Eric Goepfert, Paul A. Nat Med Article Human Leukocyte Antigen class I (HLA) restricted CD8(+) T lymphocyte (CTL) responses are critical to HIV-1 control. Although HIV can evade these responses, the longer-term impact of viral escape mutants remains unclear, since these variants can also reduce intrinsic viral fitness. To address this question, we here develop a metric to determine the degree of HIV adaptation to an HLA profile. We demonstrate that transmission of viruses pre-adapted to the HLA molecules expressed in the recipient is associated with impaired immunogenicity, elevated viral load and accelerated CD4 decline. Furthermore, the extent of pre-adaptation among circulating viruses explains much of the variation in outcomes attributed to expression of certain HLA alleles. Thus, viral pre-adaptation exploits “holes” in the immune response. Accounting for these holes may be critical for vaccine strategies seeking to elicit functional responses from viral variants, and to HIV cure strategies requiring broad CTL responses to achieve successful eradication of HIV reservoirs. 2016-05-16 2016-06 /pmc/articles/PMC4899163/ /pubmed/27183217 http://dx.doi.org/10.1038/nm.4100 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Carlson, Jonathan M.
Du, Victor Y.
Pfeifer, Nico
Bansal, Anju
Tan, Vincent Y.F.
Power, Karen
Brumme, Chanson J.
Kreimer, Anat
DeZiel, Charles E.
Fusi, Nicolo
Schaefer, Malinda
Brockman, Mark A.
Gilmour, Jill
Price, Matt A.
Kilembe, William
Haubrich, Richard
John, Mina
Mallal, Simon
Shapiro, Roger
Frater, John
Harrigan, P. Richard
Ndung’u, Thumbi
Allen, Susan
Heckerman, David
Sidney, John
Allen, Todd M.
Goulder, Philip J.R.
Brumme, Zabrina L.
Hunter, Eric
Goepfert, Paul A.
Impact of Pre-adapted HIV Transmission
title Impact of Pre-adapted HIV Transmission
title_full Impact of Pre-adapted HIV Transmission
title_fullStr Impact of Pre-adapted HIV Transmission
title_full_unstemmed Impact of Pre-adapted HIV Transmission
title_short Impact of Pre-adapted HIV Transmission
title_sort impact of pre-adapted hiv transmission
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4899163/
https://www.ncbi.nlm.nih.gov/pubmed/27183217
http://dx.doi.org/10.1038/nm.4100
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