Dynamic immune responses maintain cytotoxic T lymphocyte epitope mutations in transmitted simian immunodeficiency virus variants

Dan H. Barouch; Jennifer Powers; Diana M. Truitt; Michael G. Kishko; Janelle C. Arthur; Fred W. Peyerl; Marcelo J. Kuroda; Darci A. Gorgone; Michelle A. Lifton; Carol I. Lord; Vanessa M. Hirsch; David C. Montefiore; Angela Carville; Keith G. Mansfield; Kevin J. Kunstman; Steven M. Wolinsky; Norman L. Letvin

doi:10.1038/ni1167

Dynamic immune responses maintain cytotoxic T lymphocyte epitope mutations in transmitted simian immunodeficiency virus variants

Dan H. Barouch^*, Jennifer Powers, Diana M. Truitt, Michael G. Kishko, Janelle C. Arthur, Fred W. Peyerl, Marcelo J. Kuroda, Darci A. Gorgone, Michelle A. Lifton, Carol I. Lord, Vanessa M. Hirsch, David C. Montefiore, Angela Carville, Keith G. Mansfield, Kevin J. Kunstman, Steven M. Wolinsky, Norman L. Letvin

^*Corresponding author for this work

Medicine, Infectious Diseases Division

Research output: Contribution to journal › Article › peer-review

49 Scopus citations

Abstract

Viral escape from cytotoxic T lymphocytes (CTLs) can undermine immune control of human immunodeficiency virus 1. It is therefore important to assess the stability of viral mutations in CTL epitopes after transmission to naive hosts. Here we demonstrate the persistence of mutations in a dominant CTL epitope after transmission of simian immunodeficiency virus variants to major histocompatibility complex-matched rhesus monkeys. Transient reversions to wild-type sequences occurred and elicited CTLs specific for the wild-type epitope, resulting in immunological pressure that rapidly reselected the mutant viruses. These data suggest that mutations in dominant human immunodeficiency virus 1 CTL epitopes may accumulate in human populations with limited major histocompatibility complex heterogeneity by a mechanism involving dynamic CTL control of transiently reverted wild-type virus.

Original language	English (US)
Pages (from-to)	247-252
Number of pages	6
Journal	Nature Immunology
Volume	6
Issue number	3
DOIs	https://doi.org/10.1038/ni1167
State	Published - 2005

Funding

We thank S. Sumida, J. Schmitz, S. Santra, and K. Reimann for advice, assistance and reagents. Peptides were obtained from the National Institutes of Health AIDS Research and Reference Reagent Program. Supported by US National Institutes of Health (AI-20729 to N.L.L.; AI-58727 and AI-51223 to D.H.B.; and P51 RR-00168 to the New England Primate Research Center).

ASJC Scopus subject areas

Immunology and Allergy
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/ni1167

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Barouch, D. H., Powers, J., Truitt, D. M., Kishko, M. G., Arthur, J. C., Peyerl, F. W., Kuroda, M. J., Gorgone, D. A., Lifton, M. A., Lord, C. I., Hirsch, V. M., Montefiore, D. C., Carville, A., Mansfield, K. G., Kunstman, K. J., Wolinsky, S. M., & Letvin, N. L. (2005). Dynamic immune responses maintain cytotoxic T lymphocyte epitope mutations in transmitted simian immunodeficiency virus variants. Nature Immunology, 6(3), 247-252. https://doi.org/10.1038/ni1167

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title = "Dynamic immune responses maintain cytotoxic T lymphocyte epitope mutations in transmitted simian immunodeficiency virus variants",

abstract = "Viral escape from cytotoxic T lymphocytes (CTLs) can undermine immune control of human immunodeficiency virus 1. It is therefore important to assess the stability of viral mutations in CTL epitopes after transmission to naive hosts. Here we demonstrate the persistence of mutations in a dominant CTL epitope after transmission of simian immunodeficiency virus variants to major histocompatibility complex-matched rhesus monkeys. Transient reversions to wild-type sequences occurred and elicited CTLs specific for the wild-type epitope, resulting in immunological pressure that rapidly reselected the mutant viruses. These data suggest that mutations in dominant human immunodeficiency virus 1 CTL epitopes may accumulate in human populations with limited major histocompatibility complex heterogeneity by a mechanism involving dynamic CTL control of transiently reverted wild-type virus.",

author = "Barouch, {Dan H.} and Jennifer Powers and Truitt, {Diana M.} and Kishko, {Michael G.} and Arthur, {Janelle C.} and Peyerl, {Fred W.} and Kuroda, {Marcelo J.} and Gorgone, {Darci A.} and Lifton, {Michelle A.} and Lord, {Carol I.} and Hirsch, {Vanessa M.} and Montefiore, {David C.} and Angela Carville and Mansfield, {Keith G.} and Kunstman, {Kevin J.} and Wolinsky, {Steven M.} and Letvin, {Norman L.}",

note = "Funding Information: We thank S. Sumida, J. Schmitz, S. Santra, and K. Reimann for advice, assistance and reagents. Peptides were obtained from the National Institutes of Health AIDS Research and Reference Reagent Program. Supported by US National Institutes of Health (AI-20729 to N.L.L.; AI-58727 and AI-51223 to D.H.B.; and P51 RR-00168 to the New England Primate Research Center).",

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doi = "10.1038/ni1167",

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Barouch, DH, Powers, J, Truitt, DM, Kishko, MG, Arthur, JC, Peyerl, FW, Kuroda, MJ, Gorgone, DA, Lifton, MA, Lord, CI, Hirsch, VM, Montefiore, DC, Carville, A, Mansfield, KG, Kunstman, KJ, Wolinsky, SM & Letvin, NL 2005, 'Dynamic immune responses maintain cytotoxic T lymphocyte epitope mutations in transmitted simian immunodeficiency virus variants', Nature Immunology, vol. 6, no. 3, pp. 247-252. https://doi.org/10.1038/ni1167

TY - JOUR

T1 - Dynamic immune responses maintain cytotoxic T lymphocyte epitope mutations in transmitted simian immunodeficiency virus variants

AU - Barouch, Dan H.

AU - Powers, Jennifer

AU - Truitt, Diana M.

AU - Kishko, Michael G.

AU - Arthur, Janelle C.

AU - Peyerl, Fred W.

AU - Kuroda, Marcelo J.

AU - Gorgone, Darci A.

AU - Lifton, Michelle A.

AU - Lord, Carol I.

AU - Hirsch, Vanessa M.

AU - Montefiore, David C.

AU - Carville, Angela

AU - Mansfield, Keith G.

AU - Kunstman, Kevin J.

AU - Wolinsky, Steven M.

AU - Letvin, Norman L.

N1 - Funding Information: We thank S. Sumida, J. Schmitz, S. Santra, and K. Reimann for advice, assistance and reagents. Peptides were obtained from the National Institutes of Health AIDS Research and Reference Reagent Program. Supported by US National Institutes of Health (AI-20729 to N.L.L.; AI-58727 and AI-51223 to D.H.B.; and P51 RR-00168 to the New England Primate Research Center).

PY - 2005

Y1 - 2005

N2 - Viral escape from cytotoxic T lymphocytes (CTLs) can undermine immune control of human immunodeficiency virus 1. It is therefore important to assess the stability of viral mutations in CTL epitopes after transmission to naive hosts. Here we demonstrate the persistence of mutations in a dominant CTL epitope after transmission of simian immunodeficiency virus variants to major histocompatibility complex-matched rhesus monkeys. Transient reversions to wild-type sequences occurred and elicited CTLs specific for the wild-type epitope, resulting in immunological pressure that rapidly reselected the mutant viruses. These data suggest that mutations in dominant human immunodeficiency virus 1 CTL epitopes may accumulate in human populations with limited major histocompatibility complex heterogeneity by a mechanism involving dynamic CTL control of transiently reverted wild-type virus.

AB - Viral escape from cytotoxic T lymphocytes (CTLs) can undermine immune control of human immunodeficiency virus 1. It is therefore important to assess the stability of viral mutations in CTL epitopes after transmission to naive hosts. Here we demonstrate the persistence of mutations in a dominant CTL epitope after transmission of simian immunodeficiency virus variants to major histocompatibility complex-matched rhesus monkeys. Transient reversions to wild-type sequences occurred and elicited CTLs specific for the wild-type epitope, resulting in immunological pressure that rapidly reselected the mutant viruses. These data suggest that mutations in dominant human immunodeficiency virus 1 CTL epitopes may accumulate in human populations with limited major histocompatibility complex heterogeneity by a mechanism involving dynamic CTL control of transiently reverted wild-type virus.

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Dynamic immune responses maintain cytotoxic T lymphocyte epitope mutations in transmitted simian immunodeficiency virus variants

Abstract

Funding

ASJC Scopus subject areas

UN SDGs

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