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Journal of Virology, November 2007, p. 11703-11712, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.00926-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Pol-Specific CD8+ T Cells Recognize Simian Immunodeficiency Virus-Infected Cells Prior to Nef-Mediated Major Histocompatibility Complex Class I Downregulation{triangledown}

Jonah B. Sacha,1,{dagger} Chungwon Chung,1,{dagger} Jason Reed,1 Anna K. Jonas,1 Alexander T. Bean,1 Sean P. Spencer,1 Wonhee Lee,1 Lara Vojnov,1 Richard Rudersdorf,1 Thomas C. Friedrich,1 Nancy A. Wilson,1 Jeffrey D. Lifson,2 and David I. Watkins1,3*

Wisconsin National Primate Research Center, Madison, Wisconsin 53715,1 AIDS Vaccine Program, Science Applications International Corp., National Cancer Institute, Frederick, Maryland 21702,2 Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison, Wisconsin 537153

Received 30 April 2007/ Accepted 2 August 2007

Effective, vaccine-induced CD8+ T-cell responses should recognize infected cells early enough to prevent production of progeny virions. We have recently shown that Gag-specific CD8+ T cells recognize simian immunodeficiency virus-infected cells at 2 h postinfection, whereas Env-specific CD8+ T cells do not recognize infected cells until much later in infection. However, it remains unknown when other proteins present in the viral particle are presented to CD8+ T cells after infection. To address this issue, we explored CD8+ T-cell recognition of epitopes derived from two other relatively large virion proteins, Pol and Nef. Surprisingly, infected cells efficiently presented CD8+ T-cell epitopes from virion-derived Pol proteins within 2 h of infection. In contrast, Nef-specific CD8+ T cells did not recognize infected cells until 12 h postinfection. Additionally, we show that SIVmac239 Nef downregulated surface major histocompatibility complex class I (MHC-I) molecules beginning at 12 h postinfection, concomitant with presentation of Nef-derived CD8+ T-cell epitopes. Finally, Pol-specific CD8+ T cells eliminated infected cells as early as 6 h postinfection, well before MHC-I downregulation, suggesting a previously underappreciated antiviral role for Pol-specific CD8+ T cells.

* Corresponding author. Mailing address: Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, 555 Science Drive, Madison, WI 53711. Phone: (608) 265-3380. Fax: (608) 265-8084. E-mail: watkins{at}primate.wisc.edu

{triangledown} Published ahead of print on 15 August 2007.

{dagger} J.B.S. and C.C. contributed equally to this work.

Journal of Virology, November 2007, p. 11703-11712, Vol. 81, No. 21
0022-538X/07/$08.00+0     doi:10.1128/JVI.00926-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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