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Journal of Virology, June 2009, p. 5442-5450, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.00106-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Differential Effect of Human Herpesvirus 6A on Cell Division and Apoptosis among Naïve and Central and Effector Memory CD4⁺ and CD8⁺ T-Cell Subsets

Sudhir Gupta,^* Sudhanshu Agrawal, and Sastry Gollapudi

Division of Basic and Clinical Immunology, University of California, Irvine, California

Received 14 January 2009/ Accepted 13 March 2009

The immune responses of naive and different memory subsets of CD4⁺ and CD8⁺ T cells to human herpesvirus 6 (HHV-6) have not been previously investigated. We show that HHV-6A induces cell division, as measured by 5,6-carboxyfluorescein succinimidyl ester dye and flow cytometry, predominantly in two populations of effector memory CD4⁺ and CD8⁺ T cells (T_EM and T_EMRA); naïve (T_N) and central memory (T_CM) CD4⁺ and CD8⁺ T cells showed almost no cell division. In contrast, HHV-6A induced apoptosis primarily in T_N and T_CM CD4⁺ and CD8⁺ T cells, whereas T_EM and T_EMRA CD4⁺ and CD8⁺ T cells were resistant to HHV-6A-induced apoptosis. HHV-6A-induced apoptosis was associated with activation of caspase-8, caspase-9, and caspase-3, suggesting the involvement of death receptor and mitochondrial signaling pathways. In addition, HHV-6A induced secretion of interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-), IL-8, and gamma interferon by peripheral blood mononuclear cells; TNF- secretion was observed exclusively from CCR7⁺ (T_N plus T_CM) CD4⁺ T cells. These data show that HHV-6 differentially influences the functions of naïve T cells and different subsets of memory CD4⁺ and CD8⁺ T cells, which in part may be due to differential susceptibility to HHV-6A-induced apoptosis.

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* Corresponding author. Mailing address: Medical Sciences I, C-240, University of California, Irvine, CA 92697. Phone: (949) 824-5818. Fax: (949) 824-4362. E-mail: sgupta{at}uci.edu

Published ahead of print on 18 March 2009.

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Journal of Virology, June 2009, p. 5442-5450, Vol. 83, No. 11
0022-538X/09/$08.00+0     doi:10.1128/JVI.00106-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.