Virus-specific cytotoxic T-lymphocyte responses select for amino-acid variation in simian immunodeficiency virus Env and Nef

David T. Evans; David H. O'Connor; Peicheng Jing; John L. Dzuris; John Sidney; Jack Da Silva; Todd M. Allen; Helen Horton; John E. Venham; Richard A. Rudersdorf; Thorsten Vogel; C. David Pauza; Ronald E. Bontrop; Robert Demars; Alessandro Sette; Austin L. Hughes; David I. Watkins

doi:10.1038/15224

Virus-specific cytotoxic T-lymphocyte responses select for amino-acid variation in simian immunodeficiency virus Env and Nef

David T. Evans, David H. O'Connor, Peicheng Jing, John L. Dzuris, John Sidney, Jack Da Silva, Todd M. Allen, Helen Horton, John E. Venham, Richard A. Rudersdorf, Thorsten Vogel, C. David Pauza, Ronald E. Bontrop, Robert Demars, Alessandro Sette, Austin L. Hughes, David I. Watkins

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

357 Scopus citations

Abstract

Cytotoxic T-lymphocyte (CTL) responses to human immunodeficiency virus arise early after infection, but ultimately fail to prevent progression to AIDS. Human immunodeficiency virus may evade the CTL response by accumulating amino-acid replacements within CTL epitopes. We studied 10 CTL epitopes during the course of simian immunodeficiency virus disease progression in three related macaques. All 10 of these CTL epitopes accumulated amino-acid replacements and showed evidence of positive selection by the time the macaques died. Many of the amino-acid replacements in these epitopes reduced or eliminated major histocompatibility complex class I binding and/or CTL recognition. These findings strongly support the CTL 'escape' hypothesis.

Original language	English (US)
Pages (from-to)	1270-1276
Number of pages	7
Journal	Nature medicine
Volume	5
Issue number	11
DOIs	https://doi.org/10.1038/15224
State	Published - Nov 1999
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1038/15224

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Evans, D. T., O'Connor, D. H., Jing, P., Dzuris, J. L., Sidney, J., Da Silva, J., Allen, T. M., Horton, H., Venham, J. E., Rudersdorf, R. A., Vogel, T., Pauza, C. D., Bontrop, R. E., Demars, R., Sette, A., Hughes, A. L., & Watkins, D. I. (1999). Virus-specific cytotoxic T-lymphocyte responses select for amino-acid variation in simian immunodeficiency virus Env and Nef. Nature medicine, 5(11), 1270-1276. https://doi.org/10.1038/15224

Virus-specific cytotoxic T-lymphocyte responses select for amino-acid variation in simian immunodeficiency virus Env and Nef. / Evans, David T.; O'Connor, David H.; Jing, Peicheng; Dzuris, John L.; Sidney, John; Da Silva, Jack; Allen, Todd M.; Horton, Helen; Venham, John E.; Rudersdorf, Richard A.; Vogel, Thorsten; Pauza, C. David; Bontrop, Ronald E.; Demars, Robert; Sette, Alessandro; Hughes, Austin L.; Watkins, David I.

In: Nature medicine, Vol. 5, No. 11, 11.1999, p. 1270-1276.

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

Evans, DT, O'Connor, DH, Jing, P, Dzuris, JL, Sidney, J, Da Silva, J, Allen, TM, Horton, H, Venham, JE, Rudersdorf, RA, Vogel, T, Pauza, CD, Bontrop, RE, Demars, R, Sette, A, Hughes, AL & Watkins, DI 1999, 'Virus-specific cytotoxic T-lymphocyte responses select for amino-acid variation in simian immunodeficiency virus Env and Nef', Nature medicine, vol. 5, no. 11, pp. 1270-1276. https://doi.org/10.1038/15224

Evans, David T. ; O'Connor, David H. ; Jing, Peicheng ; Dzuris, John L. ; Sidney, John ; Da Silva, Jack ; Allen, Todd M. ; Horton, Helen ; Venham, John E. ; Rudersdorf, Richard A. ; Vogel, Thorsten ; Pauza, C. David ; Bontrop, Ronald E. ; Demars, Robert ; Sette, Alessandro ; Hughes, Austin L. ; Watkins, David I. / Virus-specific cytotoxic T-lymphocyte responses select for amino-acid variation in simian immunodeficiency virus Env and Nef. In: Nature medicine. 1999 ; Vol. 5, No. 11. pp. 1270-1276.

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title = "Virus-specific cytotoxic T-lymphocyte responses select for amino-acid variation in simian immunodeficiency virus Env and Nef",

abstract = "Cytotoxic T-lymphocyte (CTL) responses to human immunodeficiency virus arise early after infection, but ultimately fail to prevent progression to AIDS. Human immunodeficiency virus may evade the CTL response by accumulating amino-acid replacements within CTL epitopes. We studied 10 CTL epitopes during the course of simian immunodeficiency virus disease progression in three related macaques. All 10 of these CTL epitopes accumulated amino-acid replacements and showed evidence of positive selection by the time the macaques died. Many of the amino-acid replacements in these epitopes reduced or eliminated major histocompatibility complex class I binding and/or CTL recognition. These findings strongly support the CTL 'escape' hypothesis.",

author = "Evans, {David T.} and O'Connor, {David H.} and Peicheng Jing and Dzuris, {John L.} and John Sidney and {Da Silva}, Jack and Allen, {Todd M.} and Helen Horton and Venham, {John E.} and Rudersdorf, {Richard A.} and Thorsten Vogel and Pauza, {C. David} and Bontrop, {Ronald E.} and Robert Demars and Alessandro Sette and Hughes, {Austin L.} and Watkins, {David I.}",

note = "Funding Information: Acknowledgments We thank L. Smith for help in preparing this manuscript and B. Becker for help with illustration. We thank J. Scheffler for initially identifying this family, and J. Mitchen, M. Dykhuizen and L. Acker for infecting the macaques, collecting blood and monitoring disease progression. We also thank J. Malter, S. Wolinsky and G. Watkins for critical review. This work was supported by grants from the National Institutes of Health (AI32426, AI42641, and AI41913 to D.I.W.; AI36643 to C.D.P.; AI15486 to R.D.; GM34940 to A.L.H.; AI38081 to Epimmune; and RR00167 to the Wisconsin Regional Primate Research Center). D.I.W. is an Elizabeth Glaser Scientist.",

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Virus-specific cytotoxic T-lymphocyte responses select for amino-acid variation in simian immunodeficiency virus Env and Nef

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