Chikungunya virus–induced autophagy delays caspase-dependent cell death

Joubert, Pierre-Emmanuel; Werneke, Scott; Calle, Claire de la; Guivel‐Benhassine, Florence; Giodini, Alessandra; Peduto, Lucie; Levine, Beth; Schwartz, Olivier; Lenschow, Deborah J.; Albert, Matthew L.

doi:10.1084/jem.20110996

Cited by 174 publications

(158 citation statements)

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“…These data indicate that the ability of hNDP52 to bind both hLC3-C and nsP2 is implicated in its species-specific proviral effect on CHIKV. These results reconcile the two apparently conflicting reports, which showed that autophagy plays an antiviral role in mouse cells [27] but a proviral role in human cells [28]. Moreover, these results suggest that the lower permissiveness to CHIKV of the mouse relative to humans [29] might result, at least in part, from the absence of the proviral role of NDP52 in the mouse.…”

Section: Ndp52-nsp2 Interaction Is Species Specificsupporting

confidence: 84%

“…Autophagy plays an antiviral role in CHIKV-infected mouse cells [27] and a proviral role in CHIKV-infected human cells [28]. To better understand these apparently conflicting results, we investigated the role of mouse NDP52 (mNDP52).…”

Section: Ndp52-nsp2 Interaction Is Species Specificmentioning

confidence: 99%

“…Autophagy might exert anti-or pro-viral roles and its impact on alphaviruses has been investigated [23][24][25][26]. Autophagy has been reported to limit the pathogenesis of CHIKV-infected mouse cells [27]. Yet, in human cultured cells, CHIKV triggers an autophagic response that promotes viral replication [28].…”

Section: Introductionmentioning

confidence: 99%

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Species‐specific impact of the autophagy machinery on Chikungunya virus infection

et al. 2013

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Chikungunya virus (CHIKV) is a recently re-emerged arbovirus that triggers autophagy. Here, we show that CHIKV interacts with components of the autophagy machinery during its replication cycle, inducing a cytoprotective effect. The autophagy receptor p62 protects cells from death by binding ubiquitinated capsid and targeting it to autophagolysosomes. By contrast, the human autophagy receptor NDP52-but not its mouse orthologueinteracts with the non-structural protein nsP2, thereby promoting viral replication. These results highlight the distinct roles of p62 and NDP52 in viral infection, and identify NDP52 as a cellular factor that accounts for CHIKV species specificity.

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Section: Ndp52-nsp2 Interaction Is Species Specificsupporting

confidence: 84%

Section: Ndp52-nsp2 Interaction Is Species Specificmentioning

confidence: 99%

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Species‐specific impact of the autophagy machinery on Chikungunya virus infection

et al. 2013

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“…1 Autophagy is a lysosome-dependent bulk degradation pathway, which controls the clearance and recycling of cytoplasmic components for the maintenance of cellular survival. 2 Autophagy includes at least 3 pathways: macroautophagy, microautophagy, and chaperone-mediated autophagy. 2 Of these, macroautophagy is the most prevalent form of autophagy and has been implicated in cardiovascular diseases.…”

mentioning

confidence: 99%

“…2 Autophagy includes at least 3 pathways: macroautophagy, microautophagy, and chaperone-mediated autophagy. 2 Of these, macroautophagy is the most prevalent form of autophagy and has been implicated in cardiovascular diseases. 3 In the present study, macroautophagy will be referred to as autophagy.…”

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confidence: 99%

ATG16L1 phosphorylation is oppositely regulated by CSNK2/casein kinase 2 and PPP1/protein phosphatase 1 which determines the fate of cardiomyocytes during hypoxia/reoxygenation

Song¹,

Wang³

et al. 2015

Autophagy

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(2015) ATG16L1 phosphorylation is oppositely regulated by CSNK2/casein kinase 2 and PPP1/protein phosphatase 1 which determines the fate of cardiomyocytes during hypoxia/reoxygenation, Autophagy, 11:8, 1308-1325, DOI: 10.1080/15548627.2015 Keywords: ATG16L1, autophagy, cardiomyocyte, casein kinase 2, protein phosphatase 1 Abbreviations: ACTB, actinb; AMPK, AMP activated protein kinase; ATG, autophagy-related; BCL2, B-cell CLL/lymphoma 2; BECN1/Beclin 1, autophagy related; CD, Crohn disease; CSNK2, casein kinase 2; GFP, green fluorescent protein; GNB2L1/ RACK1, guanine nucleotide binding protein (G protein)bpolypeptide 2-like 1; GST, glutathione S-transferase; H/R, hypoxia/reoxygenation; I/R, ischemia/reperfusion; LAD, left anterior descending; MAP1LC3B/LC3B, microtubule-associated protein 1 light chain 3 b; mRFP, monomeric red fluorescent protein; MTORC1, mechanistic target of rapamycin complex 1; NRVCs, neonatal rat ventricular cardiomyocytes; OA, okadaic acid; PE, phosphatidylethanolamine; PPP1, protein phosphatase 1; PPP2, protein phosphatase 2; PVDF, polyvinylidenedifluoride; SNP, single nucleotide polymorphism; SUPT20H/p38IP, suppressor of Ty 20 homolog (S. cerevisiae); TBB, 4,5,6,7-tetrabromobenzotriazole; lPP, l protein phosphatase.Recent studies have shown that the phosphorylation and dephosphorylation of ULK1 and ATG13 are related to autophagy activity. Although ATG16L1 is absolutely required for autophagy induction by affecting the formation of autophagosomes, the post-translational modification of ATG16L1 remains elusive. Here, we explored the regulatory mechanism and role of ATG16L1 phosphorylation for autophagy induction in cardiomyocytes. We showed that ATG16L1 was a phosphoprotein, because phosphorylation of ATG16L1 was detected in rat cardiomyocytes during hypoxia/ reoxygenation (H/R). We not only demonstrated that CSNK2 (casein kinase 2) phosphorylated ATG16L1, but also identified the highly conserved Ser139 as the critical phosphorylation residue for CSNK2. We further established that ATG16L1 associated with the ATG12-ATG5 complex in a Ser139 phosphorylation-dependent manner. In agreement with this finding, CSNK2 inhibitor disrupted the ATG12-ATG5-ATG16L1 complex. Importantly, phosphorylation of ATG16L1 on Ser139 was responsible for H/R-induced autophagy in cardiomyocytes, which protects cardiomyocytes from apoptosis. Conversely, we determined that wild-type PPP1 (protein phosphatase 1), but not the inactive mutant, associated with ATG16L1 and antagonized CSNK2-mediated phosphorylation of ATG16L1. Interestingly, one RVxF consensus site for PPP1 binding in the C-terminal tail of ATG16L1 was identified; mutation of this site disrupted its association with ATG16L1. Notably, CSNK2 also associated with PPP1, but ATG16L1 depletion impaired the interaction between CSNK2 and PPP1. Collectively, these data identify ATG16L1 as a bona fide physiological CSNK2 and PPP1 substrate, which reveals a novel molecular link from CSNK2 to activation of the autophagy-specific ATG12-ATG5-ATG16L1 complex and autoph...

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Autophagy in Immune Responses to Viruses

Viret

Faure

2014

Autophagy, Infection, and the Immune Response

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Chikungunya virus–induced autophagy delays caspase-dependent cell death

Abstract: Chikungunya virus induces autophagy by triggering ER and oxidative stress, and this autophagy restricts apoptosis and viral propagation.

Cited by 174 publications

References 74 publications

Species‐specific impact of the autophagy machinery on Chikungunya virus infection

Species‐specific impact of the autophagy machinery on Chikungunya virus infection

ATG16L1 phosphorylation is oppositely regulated by CSNK2/casein kinase 2 and PPP1/protein phosphatase 1 which determines the fate of cardiomyocytes during hypoxia/reoxygenation

Autophagy in Immune Responses to Viruses

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