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

Robichaud, Gilles A.; Barbeau, Benoı̂t; Fortin, Jean-François; Rothstein, David M.; Tremblay, Michel J.

doi:10.1074/jbc.m201563200

Cited by 35 publications

(23 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…44 Antibodymediated engagement of the TCR/CD3 complex and host-cell attachment by HIV-1 virions ectopically expressing CD86 can synergize to activate NFAT-stimulated HIV-1 LTR transcription. 45 Also, consistent with the previous finding that NFAT levels are upregulated in memory/effector CD4T cells, 11 NFAT1 was recently identified as a major factor responsible for the preferential replication of HIV-1 in CD45RO þ 'memory' T lymphocytes, 46 a potential reservoir of latently infected cells. Interestingly, NFAT-driven HIV-1 LTR transcription Method by which the effect of this site was examined.…”

Section: Nfat and Hiv-1 F Pessler And Rq Cronsupporting

confidence: 78%

Reciprocal regulation of the nuclear factor of activated T cells and HIV-1

Peßler

Cron

2004

Genes Immun

View full text Add to dashboard Cite

The human immunodeficiency virus type 1 (HIV-1) has evolved to coordinate its replication with the activation state of the host CD4T cell. To this end, it taps into major host cell signaling pathways and their associated transcription factors. Of these, T-cell activation and the transcription factor NF-kB, respectively, have become the best-studied examples. The past several years have revealed compelling evidence that another transcription factor family involved in T-cell activation, the nuclear factor of activated T cells (NFAT), plays an important role in the regulation of HIV-1. Major advances have been made in our understanding of the interaction of HIV-1 with this intriguing transcription factor. The duplicated NF-kB binding sites in the HIV-1 enhancer surprisingly also bind NFAT proteins and appear to be the most important targets for NFAT transactivation of the HIV-1 long terminal repeat. The crystal structure of NFAT1 bound to one of these duplicated sites was solved recently. Interestingly, it showed that NFAT1 binds to this site as a homodimer and occupies the core of the NF-kB site, suggesting mutually exclusive binding and alternate transactivation by these two factors. NFAT also regulates HIV-1 infection indirectly, as it can relieve a block to reverse transcription in quiescent T cells. In turn, HIV-1, and particularly its Tat and Nef gene products, can upregulate NFAT expression and activity. This reciprocal regulation between virus and transcription factor potentially creates a positive feedback loop, which may facilitate the establishment of early HIV-1 infection and, later, the transition from latent to productive infection. The immunosuppressive drug cyclosporin A (CsA) inhibits NFAT activity and thus represents a potential treatment for HIV-1 infection. Recent small-scale clinical trials have yielded optimistic results, suggesting roles for CsA after organ transplantation in HIV-1 þ individuals and as adjunct treatment in stable early HIV-1 infection.

show abstract

Section: Nfat and Hiv-1 F Pessler And Rq Cronsupporting

confidence: 78%

Reciprocal regulation of the nuclear factor of activated T cells and HIV-1

Peßler

Cron

2004

Genes Immun

View full text Add to dashboard Cite

show abstract

“…Independent studies have shown that selective NFAT activation produces a phenotype similar to that of EC stimulation in HIV-infected T cells. NFAT-driven HIV production leads to preferential infection of memory T cells (50), and viral replication occurs without T-cell proliferation, activation marker expression, or cytokine expression (26). Lastly, selective NFAT activation, like HIV replication in our system, can be augmented by EC-specific factors.…”

Section: Discussionmentioning

confidence: 98%

Endothelial Cells Promote Human Immunodeficiency Virus Replication in Nondividing Memory T Cells via Nef-, Vpr-, and T-Cell Receptor-Dependent Activation of NFAT

Choi

Walker²,

Talbert-Slagle³

et al. 2005

J Virol

View full text Add to dashboard Cite

“…It is well-known that HIV-1 replicates preferentially in effector and memory CD4 ϩ T cells and cells displaying a naive phenotype do not support virus gene expression (51). This inability to allow virus replication seems to be linked with the absence of NFAT in naive CD4 ϩ T cells (65,(67)(68)(69). It was previously demonstrated that NFAT acts in synergy with NF-B to promote HIV-1 replication in activated and memory CD4 ϩ T cells.…”

Section: Discussionmentioning

confidence: 99%

TLR2 Signaling Renders Quiescent Naive and Memory CD4+ T Cells More Susceptible to Productive Infection with X4 and R5 HIV-Type 1

Thibault

Tardif

Barat

et al. 2007

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

It has been recently demonstrated that circulating microbial products are responsible for a systemic immune activation in individuals infected with HIV-type 1. Bacterial products carry structural conserved motifs recognized by TLRs. Some TLR members are expressed in primary human CD4+ T cells but the precise functional role played by these pattern recognition receptors is still imprecise. In this study, we report that engagement of TLR2 in quiescent naive and memory CD4+ T cells leads to the acquisition of an effector-like phenotype. Interestingly, engagement of TLR2 renders both cell subsets more susceptible to productive infection with X4 virions and a higher virus production was seen with R5 viruses. It can be proposed that exposure of resting CD4+ T cells to pathogen-derived products that can engage TLR2 induces the acquisition of an effector-like phenotype in naive and memory CD4+ T lymphocytes, a phenomenon that might result in an acceleration of virus replication, immune dysregulation, and HIV-type 1-mediated disease progression.

show abstract

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

Cited by 35 publications

References 66 publications

Reciprocal regulation of the nuclear factor of activated T cells and HIV-1

Reciprocal regulation of the nuclear factor of activated T cells and HIV-1

Endothelial Cells Promote Human Immunodeficiency Virus Replication in Nondividing Memory T Cells via Nef-, Vpr-, and T-Cell Receptor-Dependent Activation of NFAT

TLR2 Signaling Renders Quiescent Naive and Memory CD4+ T Cells More Susceptible to Productive Infection with X4 and R5 HIV-Type 1

Contact Info

Product

Resources

About