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Journal of Virology, August 2007, p. 8009-8015, Vol. 81, No. 15
0022-538X/07/$08.00+0     doi:10.1128/JVI.00482-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Memory CD4+ T-Lymphocyte Loss and Dysfunction during Primary Simian Immunodeficiency Virus Infection{triangledown}

Yue Sun, Sallie R. Permar, Adam P. Buzby, and Norman L. Letvin*

Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115

Received 7 March 2007/ Accepted 16 May 2007

It has long been appreciated that CD4+ T lymphocytes are dysfunctional in human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV)-infected individuals, and it has recently been shown that HIV/SIV infections are associated with a dramatic early destruction of memory CD4+ T lymphocytes. However, the relative contributions of CD4+ T-lymphocyte dysfunction and loss to immune dysregulation during primary HIV/SIV infection have not been fully elucidated. In the current study, we evaluated CD4+ T lymphocytes and their functional repertoire during primary SIVmac251 infection in rhesus monkeys. We show that the extent of loss of memory CD4+ T lymphocytes and staphylococcal enterotoxin B-stimulated cytokine production by total CD4+ T lymphocytes during primary SIVmac251 infection is tightly linked in a cohort of six rhesus monkeys to set point plasma viral RNA levels, with greater loss and dysfunction being associated with higher steady-state viral replication. Moreover, in exploring the mechanism underlying this phenomenon, we demonstrate that the loss of functional CD4+ T lymphocytes during primary SIVmac251 infection is associated with both a selective depletion of memory CD4+ T cells and a loss of the functional capacity of the memory CD4+ T lymphocytes that escape viral destruction.

* Corresponding author. Mailing address: Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, RE113, P.O. Box 15732, Boston, MA 02215. Phone: (617) 667-2766. Fax: (617) 667-8210. E-mail: nletvin{at}bidmc.harvard.edu

{triangledown} Published ahead of print on 23 May 2007.

Journal of Virology, August 2007, p. 8009-8015, Vol. 81, No. 15
0022-538X/07/$08.00+0     doi:10.1128/JVI.00482-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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