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Journal of Virology, August 1999, p. 6430-6435, Vol. 73, No. 8
0022-538X/99/$04.00+0

Both Memory and CD45RA+/CD62L+ Naive CD4+ T Cells Are Infected in Human Immunodeficiency Virus Type 1-Infected Individuals

Mario A. Ostrowski,* Tae-Wook Chun, Shawn J. Justement, Ivette Motola, Michael A. Spinelli, Joseph Adelsberger, Linda A. Ehler, Stephanie B. Mizell, Claire W. Hallahan, and Anthony S. Fauci

Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892

Received 2 November 1998/Accepted 12 April 1999

Cellular activation is critical for the propagation of human immunodeficiency virus type 1 (HIV-1) infection. It has been suggested that truly naive CD4+ T cells are resistant to productive HIV-1 infection because of their constitutive resting state. Memory and naive CD4+ T-cell subsets from 11 HIV-1-infected individuals were isolated ex vivo by a combination of magnetic bead depletion and fluorescence-activated cell sorting techniques with stringent criteria of combined expression of CD45RA and CD62L to identify naive CD4+ T-cell subsets. In all patients HIV-1 provirus could be detected within naive CD45RA+/CD62L+ CD4+ T cells; in addition, replication-competent HIV-1 was isolated from these cells upon CD4+ T-cell stimulation in tissue cultures. Memory CD4+ T cells had a median of fourfold more replication-competent virus and a median of sixfold more provirus than naive CD4+ T cells. Overall, there was a median of 16-fold more integrated provirus identified in memory CD4+ T cells than in naive CD4+ T cells within a given patient. Interestingly, there was a trend toward equalization of viral loads in memory and naive CD4+ T-cell subsets in those patients who harbored CXCR4-using (syncytium-inducing) viruses. Within any given patient, there was no selective usage of a particular coreceptor by virus isolated from memory versus naive CD4+ T cells. Our findings suggest that naive CD4+ T cells may be a significant viral reservoir for HIV, particularly in those patients harboring CXCR4-using viruses.

* Corresponding author. Mailing address: Laboratory of Immunoregulation, NIAID, NIH, Building 10, Room 6A11, 9000 Rockville Pike, Bethesda, MD 20892. Phone: (301) 402-2618. Fax: (301) 402-4122. E-mail: mostrowski{at}nih.gov.

Journal of Virology, August 1999, p. 6430-6435, Vol. 73, No. 8
0022-538X/99/$04.00+0


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