Preferential replication of HIV-1 in memory CD4+ subpopulation

Cayota, Alfonso; Vuillier, Françoise; Scott‐Algara, Daniel; Dighiero, Guillaume

doi:10.1016/0140-6736(90)92311-5

Cited by 22 publications

(15 citation statements)

References 3 publications

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“…production of HXB-LUC particles. These results have also been previously reported by other groups using primary naive T cells in vivo (16,18,20,22,54). Also, syncytium formation in HIV-1-infected cells occurred exclusively in CD45RO T cells activated by anti-CD3/anti-CD28 treatment.…”

Section: Higher Hiv-1 Ltr Activation and Hiv-1 Replication In Cd45ro-supporting

confidence: 77%

Nuclear Factor of Activated T Cells Is a Driving Force for Preferential Productive HIV-1 Infection of CD45RO-expressing CD4+ T Cells

Robichaud

Barbeau

Fortin

et al. 2002

Journal of Biological Chemistry

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Human immunodeficiency virus type-1 (HIV-1) preferentially replicates in CD4-expressing T cells bearing a "memory" (CD45RO؉) rather than a "naive" (CD45RA؉/ CD62L؉) phenotype. Yet the basis for the higher susceptibility of these cells to HIV-1 infection remains unclear. Because the nature of the CD45 isoform itself can affect biochemical events in T cells, we set out to determine whether these isoforms could differently modulate HIV-1 long terminal repeat (LTR) activity and thereby replication. Through the use of CD4؉ Jurkat T cells specifically expressing distinct CD45 isoforms (i.e. CD45RABC or CD45RO), we demonstrated that a difference in CD45 isoform expression conferred preferential replication of HIV-1 to CD45RO-expressing T cell clones following a physiological CD3/CD28 stimulation. Closer analysis indicated that higher HIV-1 LTR activation levels were consistently observed in CD45RO-positive cells, which was paralleled by more pronounced nuclear factor of activated T cells (NFAT) activation in these same cells. Specific involvement of NFAT1 was revealed in studied Jurkat clones by mobility shift analyses. In addition, preferential activation of the LTR and viral replication in CD45RO T cells was FK506-and cyclosporin A-sensitive. These results underscore the importance of NFAT in HIV-1 regulation and for the first time identify the role of the CD45 isoform in limiting productive HIV-1 replication to the human CD4 memory T cell subset.

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Section: Higher Hiv-1 Ltr Activation and Hiv-1 Replication In Cd45ro-supporting

confidence: 77%

Nuclear Factor of Activated T Cells Is a Driving Force for Preferential Productive HIV-1 Infection of CD45RO-expressing CD4+ T Cells

Robichaud

Barbeau

Fortin

et al. 2002

Journal of Biological Chemistry

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“…Previous studies (12)(13)(14)25) revealed that naïve CD4 T cells are intrinsically resistant to X4 HIV replication when stimulated with anti-CD3͞CD28. This mode of stimulation induces significant cellular proliferation in the absence of HIV replication, even though the cells are infected with the virus.…”

Section: Discussionmentioning

confidence: 99%

“…Memory cells can be further divided into a number of subsets, including M1 (CD45RA ). We and others (12)(13)(14)(15) have shown that naïve T cells support productive X4 HIV infection much less efficiently than memory T cells after CD3͞CD28 stimulation.…”

mentioning

confidence: 99%

Naïve CD4 T cells inhibit CD28-costimulated R5 HIV replication in memory CD4 T cells

Mengozzi

Malipatlolla

Rosa

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

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Stimulation with antibodies to CD3 and CD28 coimmobilized on beads can be used to significantly expand T cells ex vivo. With CD4 T cells from HIV-infected patients, this expansion usually is accompanied by complete suppression of viral replication, presumed to be caused by down-regulation of the viral coreceptor CCR5 and up-regulation of CCR5 ligands. Here we show that this suppression occurs in total CD4 T cells acutely infected with R5 HIV, but not in purified CD62L ؊ memory CD4 T cells. The lack of complete suppression in these memory cells, typically comprising 10 -40% of total CD4 T cells, occurs despite high levels of CCR5 ligand secretion and down-regulation of CCR5. Significantly, adding back naïve or CD62L ؉ memory CD4 T cells inhibits the viral replication in the CD62L ؊ cells, with the naïve cells capable of completely repressing the virus. Although this inhibition was previously thought to be specific to bead-bound anti-CD3͞CD28 stimulation, we show that the same suppression is obtained with sufficiently strong anti-CD3͞B7.1 stimulation. Our results show that inhibitory mechanisms, expressed predominantly by strongly stimulated naïve CD4 T cells and mediated independently of CCR5-binding chemokines, play a role in the inhibition of R5 HIV replication in CD4 T cells upon CD28 costimulation. In contrast to these observations, Levine et al. (6) reported that stimulation of CD4 T cells of HIV-infected patients with anti-CD3 and anti-CD28 coimmobilized on Sepharose beads ''clears'' HIV from infected cultures, allowing ex vivo expansion of autologous CD4 T cells in the absence of antiretroviral drugs. The same authors later reported that this mode of stimulation decreases expression of the main HIV coreceptor CCR5 (7) and induces high levels of the HIV-inhibitory CCR5 ligands RANTES, macrophage inflammatory protein (MIP)-1␣, and MIP-1␤ (hereafter, CCR5 ligands) (8), that block access to CCR5, resulting in inhibition of CCR5-dependent (R5), but not of CXCR4-dependent (X4), HIV replication.Therefore, anti-CD3͞CD28 stimulation can result in decreased or enhanced HIV replication, apparently depending on the mode of stimulation [i.e., soluble Abs vs. Abs immobilized on beads (3, 6)]. The differential effects of these modes of stimulation on CCR5 expression and CCR5 ligand secretion do not appear to resolve the controversy. Creson et al. (9) reported that continuous passage of CD4 T cells on plastic culture dishes coated with anti-CD3͞CD28 Abs failed to inhibit R5 HIV infection, despite decreased expression of CCR5 and secretion of CCR5 ligands at levels comparable to those achieved by stimulation with anti-CD3͞CD28 mAb-conjugated beads.Our findings indicate that the resolution of this paradox lies in the strength of T cell stimulation and in the heterogeneity of CD4 T cells. CD4 T cells can be divided into naïve T cells that express both CD45RA and CD62L and memory T cells (10, 11). Memory cells can be further divided into a number of subsets, including M1 (CD45RA). We and others (12-15) have shown that naïve...

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“…Naive T cells have previously been shown to be mildly resistant to HIV infection in vitro and to harbor less virus in infected patients in vivo (4)(5)(6). However, these studies used only CD45RA or CD45RO to distinguish naive from memory T cells.…”

Section: Introductionmentioning

confidence: 99%

HIV does not replicate in naive CD4 T cells stimulated with CD3/CD28.

Roederer

Raju²,

Mitra³

et al. 1997

J. Clin. Invest.

114

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In this report, we demonstrate that the T cell tropic strain of HIV, LAI, does not replicate in naive CD4 T cells stimulated by cross-linking CD3 and CD28. In contrast, LAI replicates well in memory CD4 T cells stimulated in the same way. Unlike this physiologically relevant stimulation, PHA stimulates productive LAI replication in both naive and memory T cells. These studies were conducted with highly purified (

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Preferential replication of HIV-1 in memory CD4+ subpopulation

Cited by 22 publications

References 3 publications

Nuclear Factor of Activated T Cells Is a Driving Force for Preferential Productive HIV-1 Infection of CD45RO-expressing CD4+ T Cells

Nuclear Factor of Activated T Cells Is a Driving Force for Preferential Productive HIV-1 Infection of CD45RO-expressing CD4+ T Cells

Naïve CD4 T cells inhibit CD28-costimulated R5 HIV replication in memory CD4 T cells

HIV does not replicate in naive CD4 T cells stimulated with CD3/CD28.

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