Identifying the Target Cell in Primary Simian Immunodeficiency Virus (SIV) Infection: Highly Activated Memory CD4+ T Cells Are Rapidly Eliminated in Early SIV Infection In Vivo

doi:10.1128/JVI.74.1.57-64.2000

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Journal of Virology, January 2000, p. 57-64, Vol. 74, No. 1
0022-538X/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Identifying the Target Cell in Primary Simian Immunodeficiency Virus (SIV) Infection: Highly Activated Memory CD4⁺ T Cells Are Rapidly Eliminated in Early SIV Infection In Vivo

Ronald S. Veazey,^* Irene C. Tham, Keith G. Mansfield, MaryAnn DeMaria, Amy E. Forand, Daniel E. Shvetz, Laura V. Chalifoux, Prabhat K. Sehgal, and Andrew A. Lackner

New England Regional Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772

Received 3 May 1999/Accepted 21 September 1999

It has recently been shown that rapid and profound CD4⁺ T-cell depletion occurs almost exclusively within the intestinal tractof simian immunodeficiency virus (SIV)-infected macaques withindays of infection. Here we demonstrate (by three- and four-colorflow cytometry) that this depletion is specific to a definablesubset of CD4⁺ T cells, namely, those having both a highly and/or acutely activated(CD69⁺ CD38⁺ HLA-DR⁺) and memory (CD45RA Leu8) phenotype. Moreover, we demonstrate that this subset of helperT cells is found primarily within the intestinal lamina propria.Viral tropism for this particular cell type (which has been previouslysuggested by various studies in vitro) could explain why profoundCD4⁺ T-cell depletion occurs in the intestine and not in peripherallymphoid tissues in early SIV infection. Furthermore, we demonstratethat an acute loss of this specific subset of activated memoryCD4⁺ T cells may also be detected in peripheral blood and lymph nodesin early SIV infection. However, since this particular cell typeis present in such small numbers in circulation, its loss doesnot significantly affect total CD4⁺ T cell counts. This finding suggests that SIV and, presumably,human immunodeficiency virus specifically infect, replicate in,and eliminate definable subsets of CD4⁺ T cells invivo.

^* Corresponding author. Mailing address: Division of Comparative Pathology, One Pine Hill Drive, P.O. Box 9102, Southborough,MA 01772. Phone: (508) 624-8013. Fax: (508) 624-8181. E-mail:ronald_veazey{at}hms.harvard.edu.

Journal of Virology, January 2000, p. 57-64, Vol. 74, No. 1
0022-538X/0/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

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