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Journal of Virology, June 2008, p. 5631-5635, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.02749-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Contribution of CD8+ T Cells to Containment of Viral Replication and Emergence of Mutations in Mamu-A*01-Restricted Epitopes in Simian Immunodeficiency Virus-Infected Rhesus Monkeys{triangledown} ,{dagger}

Eun-Young Kim,1* Ronald S. Veazey,2 Roland Zahn,3 Kimberly J. McEvers,3 Susanne H. C. Baumeister,3 Gabriel J. Foster,3 Melisa D. Rett,3 Michael H. Newberg,3 Marcelo J. Kuroda,2 E. Peter Rieber,4 Michael Piatak Jr.,5 Jeffrey D. Lifson,5 Norman L. Letvin,3 Steven M. Wolinsky,1 and Jörn E. Schmitz3*

Division of Infectious Diseases, The Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611,1 Tulane National Primate Research Center, Covington, Louisiana 70433,2 Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115,3 Institute of Immunology, Technical University of Dresden, 01101 Dresden, Germany,4 AIDS Vaccine Program, SAIC Fredrick, Inc., National Cancer Institute at Frederick, Frederick, Maryland 217025

Received 27 December 2007/ Accepted 11 March 2008

Here, we investigated the containment of virus replication in simian immunodeficiency virus (SIV) infection by CD8+ lymphocytes. Escape mutations in Mamu-A*01 epitopes appeared first in SIV Tat TL8 and then in SIV Gag p11C. The appearance of escape mutations in SIV Gag p11C was coincident with compensatory changes outside of the epitope. Eliminating CD8+ lymphocytes from rhesus monkeys during primary infection resulted in more rapid disease progression that was associated with preservation of canonical epitopes. These results confirm the importance of cytotoxic T cells in controlling viremia and the constraint on epitope sequences that require compensatory changes to go to fixation.

* Corresponding author. Mailing address for Eun-Young Kim: Division of Infectious Diseases, The Feinberg School of Medicine, Northwestern University, 676 N. St. Clair St., Suite 200, Chicago, IL 60611. Phone: (312) 695-5085. Fax: (312) 695-5088. E-mail: e-kim{at}northwestern.edu. Mailing address for Jörn E. Schmitz: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, RE-213D, 41 Avenue Louis Pasteur, Boston, MA 02115. Phone: (617) 667-5206. Fax: (617) 667-8210. E-mail: jschmitz{at}bidmc.harvard.edu

{triangledown} Published ahead of print on 26 March 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, June 2008, p. 5631-5635, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.02749-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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