Major histocompatibility complex class I alleles associated with slow simian immunodeficiency virus disease progression bind epitopes recognized by dominant acute-phase cytotoxic-T-lymphocyte responses

David H. O'Connor, Bianca R. Mothe, Jason T. Weinfurter, Sarah Fuenger, William M. Rehrauer, Peicheng Jing, Richard R. Rudersdorf, Max E. Liebl, Kendall Krebs, Joshua Vasquez, Elizabeth Dodds, John Loffredo, Sarah Martin, Adrian B. McDermott, Todd M. Allen, Chenxi Wang, G. G. Doxiadis, David C. Montefiori, Austin Hughes, Dennis R. Burton & 5 others David B. Allison, Steven M. Wolinsky, Ronald Bontrop, Louis J. Picker, David Watkins

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

Certain major histocompatibility complex class I (MHC-I) alleles are associated with delayed disease progression in individuals infected with human immunodeficiency virus (HIV) and in macaques infected with simian immunodeficiency virus (SIV). However, little is known about the influence of these MHC alleles on acute-phase cellular immune responses. Here we follow 51 animals infected with SIVmac239 and demonstrate a dramatic association between Mamu-A*01 and -B*17 expression and slowed disease progression. We show that the dominant acute-phase cytotoxic T lymphocyte (CTL) responses in animals expressing these alleles are largely directed against two epitopes restricted by Mamu-A*01 and one epitope restricted by Mamu-B*17. One Mamu-A*01-restricted response (Tat28-35SL8) and the Mamu-B*17-restricted response (Nef165-173IW9) typically select for viral escape variants in early SIVmac239 infection. Interestingly, animals expressing Mamu-A*1 and -B*17 have less variation in the Tat28-35SL8 epitope during chronic infection than animals that express only Mamu-A*01. Our results show that MHC-I alleles that are associated with slow progression to AIDS bind epitopes recognized by dominant CTL responses during acute infection and underscore the importance of understanding CTL responses during primary HIV infection.

Original languageEnglish
Pages (from-to)9029-9040
Number of pages12
JournalJournal of Virology
Volume77
Issue number16
DOIs
StatePublished - Aug 1 2003
Externally publishedYes

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Simian immunodeficiency virus
Simian Immunodeficiency Virus
cytotoxic T-lymphocytes
major histocompatibility complex
Cytotoxic T-Lymphocytes
Virus Diseases
Major Histocompatibility Complex
disease course
epitopes
Disease Progression
Epitopes
Alleles
alleles
Infection
HIV
infection
animals
Human immunodeficiency virus
HIV infections
Macaca

ASJC Scopus subject areas

  • Immunology

Cite this

Major histocompatibility complex class I alleles associated with slow simian immunodeficiency virus disease progression bind epitopes recognized by dominant acute-phase cytotoxic-T-lymphocyte responses. / O'Connor, David H.; Mothe, Bianca R.; Weinfurter, Jason T.; Fuenger, Sarah; Rehrauer, William M.; Jing, Peicheng; Rudersdorf, Richard R.; Liebl, Max E.; Krebs, Kendall; Vasquez, Joshua; Dodds, Elizabeth; Loffredo, John; Martin, Sarah; McDermott, Adrian B.; Allen, Todd M.; Wang, Chenxi; Doxiadis, G. G.; Montefiori, David C.; Hughes, Austin; Burton, Dennis R.; Allison, David B.; Wolinsky, Steven M.; Bontrop, Ronald; Picker, Louis J.; Watkins, David.

In: Journal of Virology, Vol. 77, No. 16, 01.08.2003, p. 9029-9040.

Research output: Contribution to journalArticle

O'Connor, DH, Mothe, BR, Weinfurter, JT, Fuenger, S, Rehrauer, WM, Jing, P, Rudersdorf, RR, Liebl, ME, Krebs, K, Vasquez, J, Dodds, E, Loffredo, J, Martin, S, McDermott, AB, Allen, TM, Wang, C, Doxiadis, GG, Montefiori, DC, Hughes, A, Burton, DR, Allison, DB, Wolinsky, SM, Bontrop, R, Picker, LJ & Watkins, D 2003, 'Major histocompatibility complex class I alleles associated with slow simian immunodeficiency virus disease progression bind epitopes recognized by dominant acute-phase cytotoxic-T-lymphocyte responses', Journal of Virology, vol. 77, no. 16, pp. 9029-9040. https://doi.org/10.1128/JVI.77.16.9029-9040.2003
O'Connor, David H. ; Mothe, Bianca R. ; Weinfurter, Jason T. ; Fuenger, Sarah ; Rehrauer, William M. ; Jing, Peicheng ; Rudersdorf, Richard R. ; Liebl, Max E. ; Krebs, Kendall ; Vasquez, Joshua ; Dodds, Elizabeth ; Loffredo, John ; Martin, Sarah ; McDermott, Adrian B. ; Allen, Todd M. ; Wang, Chenxi ; Doxiadis, G. G. ; Montefiori, David C. ; Hughes, Austin ; Burton, Dennis R. ; Allison, David B. ; Wolinsky, Steven M. ; Bontrop, Ronald ; Picker, Louis J. ; Watkins, David. / Major histocompatibility complex class I alleles associated with slow simian immunodeficiency virus disease progression bind epitopes recognized by dominant acute-phase cytotoxic-T-lymphocyte responses. In: Journal of Virology. 2003 ; Vol. 77, No. 16. pp. 9029-9040.
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AU - O'Connor, David H.

AU - Mothe, Bianca R.

AU - Weinfurter, Jason T.

AU - Fuenger, Sarah

AU - Rehrauer, William M.

AU - Jing, Peicheng

AU - Rudersdorf, Richard R.

AU - Liebl, Max E.

AU - Krebs, Kendall

AU - Vasquez, Joshua

AU - Dodds, Elizabeth

AU - Loffredo, John

AU - Martin, Sarah

AU - McDermott, Adrian B.

AU - Allen, Todd M.

AU - Wang, Chenxi

AU - Doxiadis, G. G.

AU - Montefiori, David C.

AU - Hughes, Austin

AU - Burton, Dennis R.

AU - Allison, David B.

AU - Wolinsky, Steven M.

AU - Bontrop, Ronald

AU - Picker, Louis J.

AU - Watkins, David

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