Gag- and Nef-specific CD4+ T cells recognize and inhibit SIV replication in infected macrophages early after infection

Jonah Sacha, Juan P. Giraldo-Vela, Matthew B. Buechler, Mauricio A. Martins, Nicholas J. Maness, Won Chung, Lyle T. Wallace, Enrique J. Leóna, Thomas C. Friedrich, Nancy A. Wilson, Atsunobu Hiraoka, David I. Watkins

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

The precise immunological role played by CD4+ T cells in retroviral infections is poorly defined. Here, we describe a new function of these cells, the elimination of retrovirus-infected macrophages. After experimental CD8+ cell depletion, elite controlling macaques with set-point viral loads ≤500 viral RNA copies/mL mounted robust Gag- and Nef-specific CD4+ T cell responses during reestablishment of control with ≥54% of all virus-specific CD4+ T cells targeting these 2 proteins. Ex vivo, these simian immunodeficiency virus (SIV)-specific CD4 + T cells neither recognized nor suppressed viral replication in SIV-infected CD4+ T cells. In contrast, they recognized SIV-infected macrophages as early as 2 h postinfection because of presentation of epitopes derived from virion-associated Gag and Nef proteins. Furthermore, virus-specific CD4+ T cells displayed direct effector function and eliminated SIV-infected macrophages. These results suggest that retrovirus-specific CD4+ T cells may contribute directly to elite control by inhibiting viral replication in macrophages.

Original languageEnglish (US)
Pages (from-to)9791-9796
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number24
DOIs
StatePublished - Jun 16 2009
Externally publishedYes

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Simian Immunodeficiency Virus
Virus Replication
Macrophages
T-Lymphocytes
Infection
Retroviridae
nef Gene Products
Viruses
gag Gene Products
Viral RNA
Macaca
Protein Transport
Viral Load
Virion
Epitopes

Keywords

  • Antigen processing and presentation
  • HIV

ASJC Scopus subject areas

  • General

Cite this

Gag- and Nef-specific CD4+ T cells recognize and inhibit SIV replication in infected macrophages early after infection. / Sacha, Jonah; Giraldo-Vela, Juan P.; Buechler, Matthew B.; Martins, Mauricio A.; Maness, Nicholas J.; Chung, Won; Wallace, Lyle T.; Leóna, Enrique J.; Friedrich, Thomas C.; Wilson, Nancy A.; Hiraoka, Atsunobu; Watkins, David I.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 106, No. 24, 16.06.2009, p. 9791-9796.

Research output: Contribution to journalArticle

Sacha, J, Giraldo-Vela, JP, Buechler, MB, Martins, MA, Maness, NJ, Chung, W, Wallace, LT, Leóna, EJ, Friedrich, TC, Wilson, NA, Hiraoka, A & Watkins, DI 2009, 'Gag- and Nef-specific CD4+ T cells recognize and inhibit SIV replication in infected macrophages early after infection', Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 24, pp. 9791-9796. https://doi.org/10.1073/pnas.0813106106
Sacha, Jonah ; Giraldo-Vela, Juan P. ; Buechler, Matthew B. ; Martins, Mauricio A. ; Maness, Nicholas J. ; Chung, Won ; Wallace, Lyle T. ; Leóna, Enrique J. ; Friedrich, Thomas C. ; Wilson, Nancy A. ; Hiraoka, Atsunobu ; Watkins, David I. / Gag- and Nef-specific CD4+ T cells recognize and inhibit SIV replication in infected macrophages early after infection. In: Proceedings of the National Academy of Sciences of the United States of America. 2009 ; Vol. 106, No. 24. pp. 9791-9796.
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