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

1999; American Society for Microbiology; Volume: 73; Issue: 8 Linguagem: Inglês

10.1128/jvi.73.8.6430-6435.1999

1098-5514

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

T-cell and B-cell Immunology

ABSTRACT 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.