FOXO1 transcription factor plays a key role in T cell—HIV-1 interaction

Roux, A.; Leroy, Héloïse; Muylder, Bénédicte De; Bracq, Lucie; Oussous, Samia; Dusanter‐Fourt, Isabelle; Chougui, Ghina; Tacine, Rachida; Randriamampita, Clotilde; Desjardins, Delphine; Grand, Roger Le; Bouillaud, Frédéric; Bénichou, Serge; Margottin-Goguet, Florence; Cheynier, Rémi; Bismuth, Georges; Mangeney, Marianne

doi:10.1371/journal.ppat.1007669

Cited by 24 publications

(23 citation statements)

References 54 publications

(65 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This TF is associated with a quiescent central memory T cell (Tcm) phenotype, consistent with the hypothesis that cells that adopt a quiescent Tcm phenotype are more prone to latent infection (Garaud et al, 2017). Interestingly, a related Forkhead TF, FOXO1, has also recently been reported to promote HIV latency (Roux et al, 2019;Vallejo-Gracia et al, 2020). In addition to these known HIV-regulating TFs, several TFs with no known role in HIV transcription were identified by our study, and defining their role in latency will likely lead to the discovery of new mechanisms of transcriptional repression for HIV.…”

Section: Discussionsupporting

confidence: 76%

Epigenomic characterization of latent HIV infection identifies latency regulating transcription factors

Jefferys

Burgos²,

Peterson³

et al. 2020

Preprint

View full text Add to dashboard Cite

SummaryTranscriptional silencing of HIV generates a reservoir of latently infected cells, but the mechanisms that lead to this outcome are not well understood. We characterized a primary cell model of HIV latency, and observed that latency is a stable, heritable viral state that is rapidly reestablished after stimulation. Using Assay of Transposon-Accessible Chromatin sequencing (ATACseq) we found that latently infected cells exhibit reduced proviral accessibility, elevated activity of Forkead and Kruppel-like factor transcription factors (TFs), and reduced activity of AP-1, RUNX and GATA TFs. Latency reversing agents caused distinct patterns of chromatin reopening across the provirus. Furthermore, depletion of a chromatin domain insulator, CTCF inhibited HIV latency, identifying this factor as playing a key role in the initiation or enforcement of latency. These data indicate that HIV latency develops preferentially in cells with a distinct pattern of TF activity that promotes a closed proviral structure and inhibits viral gene expression.

show abstract

Section: Discussionsupporting

confidence: 76%

Epigenomic characterization of latent HIV infection identifies latency regulating transcription factors

Jefferys

Burgos²,

Peterson³

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…These results suggested that FoxO1 may be involved in the regulation of GFAT2 expression in macrophages. To evaluate the potential involvement of FoxO1 in the regulation of GFAT2 expression, we used a small molecule specific inhibitor of FoxO1 activity, the AS1842856 drug [57]. We observed, both in RAW264.7 cells (Fig.…”

Section: Gfat2 Expression Is Dependent On Foxo1 Transcription Factor mentioning

confidence: 92%

LPS induces GFAT2 expression to promote O-GlcNAcylation and attenuate inflammation in macrophages

Al-Mukh

Baudoin

Bouaboud

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

O-GlcNAc glycosylation is a reversible post-translational modification that regulates the activity of intracellular proteins according to glucose availability and its metabolism through the hexosamine biosynthesis pathway (HBP). This modification has been involved in the regulation of various immune cell types, including macrophages. However, little is known concerning the mechanisms that regulate protein O-GlcNAcylation level in these cells. In the present work, we demonstrate that LPS treatment induces a marked increase in protein O-GlcNAcylation in RAW264.7 cells, bone-marrow-derived and peritoneal mouse macrophages, as well as human monocyte-derived macrophages. Targeted deletion of OGT in macrophages resulted in an increased effect of LPS on NOS2 expression and cytokine production, suggesting that O-GlcNAcylation may restrain inflammatory processes induced by TLR4 activation. The effect of LPS on protein O-GlcNAcylation in macrophages was associated with an increased expression and activity of glutamine fructose 6-phosphate amido-transferase (GFAT), the enzyme that catalyzes the rate-limiting step of the HBP. More specifically, we observed that LPS rapidly and potently stimulated GFAT2 isoform mRNA and protein expression. Genetic or pharmacological inhibition of FoxO1 impaired LPS effect on GFAT2 expression, suggesting a FoxO1-dependent mechanism. We conclude that GFAT2 should be considered as a new TLR4-inducible gene involved in regulation of protein O-GlcNAcylation, that permits to limit exacerbated inflammation upon macrophage activation.

show abstract

“…SAMDH1 has been reported to be a key mechanism of cell proliferation and is an essential player in dNTP homeostasis. SAMHD1 is a dNTP hydrolase which reduces the concentration of intracellular dNTP pools (52,53). It has been suggested that the inhibitory effect of SAMHD1 on HIV-1 replication is due to its dNTPase action, or it has also been suggested that SAMHD1, or an associated protein, may limit HIV-1 replication through its RNase activity (54).…”

Section: Potential Host Responses To Covid-19mentioning

confidence: 99%

“…Like other innate immunity proteins, SAMDH1 shows a crucial role in shaping innate and adaptive immunological responses to protect animals against viruses by disrupting the virus' life cycle (52). In response to that, viruses generate proteins that bind these host factors and alter their activity.…”

Section: Potential Host Responses To Covid-19mentioning

confidence: 99%

SAMHD1 as the Potential Link Between SARS-CoV-2 Infection and Neurological Complications

Khan

Sergi

2020

Front. Neurol.

View full text Add to dashboard Cite

The recent pandemic of coronavirus infectious illness 2019 (COVID19) triggered by SARS-CoV-2 has rapidly spread around the globe, generating in severe events an acute, highly lethal pneumonia and death. In the past two hitherto similar CoVs, the severe acute respiratory syndrome CoV (SARS-CoV-1) and Middle East respiratory syndrome CoV (MERS-CoV) also gained universal attention as they produced clinical symptoms similar to those of SARS-CoV-2 utilizing angiotensin-converting enzyme 2 (ACE2) receptor and dipeptidyl peptidase 4 (DPP4) to go into the cells. COVID-19 may also present with overtly neurological symptoms. The proper understanding of the expression and dissemination of ACE2 in central and peripheral nerve systems is crucial to understand better the neurological morbidity caused by COVID-19. Using the STRING bioinformatic tool and references through text mining tools associated to Coronaviruses, we identified SAMHD1 as the probable link to neurological symptoms. Paralleled to the response to influenza A virus and, specifically, respiratory syncytial virus, SARS-CoV-2 evokes a response that needs robust induction of a subclass of cytokines, including the Type I and, obviously, Type III interferons as well as a few chemokines. We correlate ACE2 to the pathogenesis and neurologic complications of COVID-19 and found that SAMHD1 links to NF-κB pathway. No correlation was found with other molecules associated with Coronavirus infection, including ADAR, BST2, IRF3, IFITM3, ISG15, MX1, MX2, RNASEL, RSAD2, and VPRBP. We suggest that SAMHD1 is the molecule that may be behind the mechanisms of the neurological complications associated with COVID-19.

show abstract

FOXO1 transcription factor plays a key role in T cell—HIV-1 interaction

Cited by 24 publications

References 54 publications

Epigenomic characterization of latent HIV infection identifies latency regulating transcription factors

Epigenomic characterization of latent HIV infection identifies latency regulating transcription factors

LPS induces GFAT2 expression to promote O-GlcNAcylation and attenuate inflammation in macrophages

SAMHD1 as the Potential Link Between SARS-CoV-2 Infection and Neurological Complications

Contact Info

Product

Resources

About