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Journal of Virology, April 2008, p. 4149-4153, Vol. 82, No. 8
0022-538X/08/$08.00+0     doi:10.1128/JVI.02242-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Expansion and Exhaustion of T-Cell Responses during Mutational Escape from Long-Term Viral Control in Two DNA/Modified Vaccinia Virus Ankara-Vaccinated and Simian-Human Immunodeficiency Virus SHIV-89.6P-Challenged Macaques{triangledown}

Shanmugalakshmi Sadagopal,2,{dagger} Rama Rao Amara,1,2 Sunil Kannanganat,1 Sunita Sharma,2,{ddagger} Lakshmi Chennareddi,2 and Harriet L. Robinson1,2,3*

Emory Vaccine Center, Emory University School of Medicine, 954 Gatewood Road, Atlanta, Georgia 30329,1 Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329,2 Department of Microbiology and Immunology of Emory University School of Medicine, Emory University, Atlanta, Georgia 303223

Received 16 October 2007/ Accepted 22 January 2008

In this study, we monitored the temporal breadths, frequencies, and functions of antiviral CD4 and CD8 T cells in 2 of 22 DNA/modified vaccinia virus Ankara-vaccinated macaques that lost control of a simian-human immunodeficiency virus 89.6P challenge by 196 weeks postchallenge. Our results show that both mutation and exhaustion contributed to escape. With the reappearance of viremia, responding CD8 and CD4 T cells underwent an initial increase and then loss of breadth and frequency. Antiviral gamma interferon (IFN-{gamma})- and interleukin 2-coproducing cells were lost before IFN-{gamma}-producing cells and CD4 cells before CD8 cells. At euthanasia, all CD8, but no CD4, Gag epitopes detected during long-term control contained mutations.

* Corresponding author. Mailing address: Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, GA 30329. Phone: (404) 727-7217. Fax: (404) 727-7768. E-mail: hrobins{at}rmy.emory.edu

{triangledown} Published ahead of print on 30 January 2008.

{dagger} Present address: Infectious Disease, Vanderbilt School of Medicine, 1161 21st Avenue, A 2200 MCN, Nashville, TN 37232.

{ddagger} Present address: DHHS/CDC/CCID/NCHHSTP/DHPSE/LB, 1600 Clifton Road, Mailstop G45, Atlanta, GA 30329-4018.

Journal of Virology, April 2008, p. 4149-4153, Vol. 82, No. 8
0022-538X/08/$08.00+0     doi:10.1128/JVI.02242-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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