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

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.

HIV-1 Vpr Enhances Viral Burden by Facilitating Infection of Tissue Macrophages but Not Nondividing CD4+ T Cells

“…Moreover, our previous studies have revealed no absolute restriction to HIV-1 infection, replication, or depletion of T cells within these cultures on the basis of target cell maturation or proliferation (47). In particular, these studies demonstrated de novo infection and depletion of resting, naive lymphocytes, which may explain the observation of productively infected resting T cells in vivo (50)(51)(52). Because these cells divide very infrequently (Fig.…”

Effects of the human CD38 glycoprotein on the early stages of the HIV‐1 replication cycle

“…The inhibition of HIV-1 replication by CD38 expression may account for the lower susceptibility of resting/ naive (CD45RA ϩ ) than memory (CD45R0 ϩ ) CD4 ϩ T cells (47)(48)(49), since resting naive cells constitutively express CD38, whereas resting memory cells are CD38 Ϫ (16). Moreover, it may play a role in the favorable prognostic value of high levels of CD38 on CD4 ϩ cells in HIV ϩ children (26) and in the relative resistance to HIV-1 infection shown by children born to a Cells were stained with FITC-conjugated gp120.…”

HIV‐1 Persistence, Viral Reservoir, and the Central Nervous System in the HAART Era

“…Replication competent HIV-1 particles were recovered after optimal non-specific activation from each of these T-lymphocyte subsets. A simultaneous study also demonstrated integrated proviral DNA in naive CD4+ CD45RA+ CD62L+ T-cells (38). The presence of integrated provirus in naive lymphocytes may result from the infection of activated thymocytes (7), from the reversion toward a naive phenotype of latently infected memory Tcells (36) or from their direct infection (43).…”