The structural proteins of epidemic and historical strains of Zika virus differ in their ability to initiate viral infection in human host cells

Bos, Sandra; Viranaïcken, Wildriss; Turpin, Jonathan; Kalamouni, Chaker El; Roche, Marjolaine; Krejbich-Trotot, Pascale; Desprès, Philippe; Gadéa, Gilles

doi:10.1016/j.virol.2017.12.003

Cited by 46 publications

(89 citation statements)

References 43 publications

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“…A549 epithelial cells have been shown to be permissive to infection by most flaviviruses [25,31] and are a suitable model for studying in cellulo host-virus interactions. Many research teams, including ours, have used this epithelial cell line to characterize ZIKV infection with different strains of the epidemic (clinical isolate PF13, molecular clone BR15) and historical (MR766) ZIKV, deciphering viral entry pathways, viral replication kinetics [32] and cellular responses such as apoptosis [33]. As protein load increases in cells replicating the virus resulting in the accumulation of misfolded or partially processed viral polyproteins and ER stress, we investigated markers of ER stress and the contribution of the Unfolded Protein Response during the course of ZIKV infection.…”

Section: Resultsmentioning

confidence: 99%

Zika Virus Envelope Protein Forms Disulfide Bond-dependent Polymers in Connection with a Persistent ER Stress in A549 Cells

Turpin¹,

Frumence²,

Harrabi³

et al. 2019

Preprint

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Flaviviruses replicate in membranous factories associated with the endoplasmic reticulum (ER). Significant levels of flavivirus polyprotein integration contribute to ER stress and the host cell may exhibit an Unfolded Protein Response (UPR) to this protein accumulation, stimulating appropriate cellular responses such as adaptation, autophagy or cell death. These different stress responses support other antiviral strategies initiated by infected cells and can help to overcome viral infection. In epithelial A549 cells, a model currently used to study the flavivirus infection cycle and the host cell responses, all three pathways leading to UPR are activated during infection by Dengue virus (DENV), Yellow Fever virus (YFV) or West Nile virus (WNV). In the present study, we investigated the capacity of ZIKA virus (ZIKV) to induce ER stress in A549 cells. We observed that the cells respond to ZIKV infection by implementing an UPR through activation of the IRE1 and PERK pathway without activation of the ATF6 branch. By modulating the ER stress response, we found that UPR inducers significantly inhibit ZIKV replication. Interestingly, our findings provide evidence that ZIKV could manipulate the UPR to escape this host cell defence system. Since incomplete UPR could lead to unresolved and persistent ER stress, we found that ZIKV infection was associated with an abnormal accumulation of viral envelope proteins, which were aggregated with non-native disulfide bridges. As the presence of these “amyloid like” protein polymers may be cytopathic, our observations provide new insights into specific neuropathologies associated with ZIKA virus infections.

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Section: Resultsmentioning

confidence: 99%

Zika Virus Envelope Protein Forms Disulfide Bond-dependent Polymers in Connection with a Persistent ER Stress in A549 Cells

Turpin¹,

Frumence²,

Harrabi³

et al. 2019

Preprint

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show abstract

“…Summary of the study Conclusions [221] ZIKV which infects neural progenitor cells in organoid and neurosphere models, activates Toll-like receptor 3 which triggers apoptosis and attenuates neurogenesis [222] Different strains of ZIKV take use of different structural proteins which affect the permissiveness of human epithelial and neuronal cells to this infection [223] Studied on SLEV; its epidemic strain; CbaAr-4005 Suggested probable entrance of SLEV to the CNS from the circulatory system, thus severe disorders induction by this infection within the central nervous system of infected mice [224] Silencing of the A. aegypti anti-apoptotic gene iap1 (Aeiap1) and silencing of initiator caspase gene, Aedronc in adult female A. aegypti mosquitoes…”

Section: Referencementioning

confidence: 99%

“…ZIKV, which infects neural progenitor cells in organoid and neurosphere models, activates Tolllike receptor 3 which triggers apoptosis and attenuates neurogenesis [221]. Different strains of ZIKV make use of different structural proteins which affects the permissiveness of human epithelial and neuronal cells to infection by this virus [222]. Saint Louis encephalitis virus (SLEV) is a neglected flavivirus.…”

Section: Referencementioning

confidence: 99%

The roles of apoptosis, autophagy and unfolded protein response in arbovirus, influenza virus, and HIV infections

Mehrbod¹,

et al. 2019

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Virus infection induces different cellular responses in infected cells. These include cellular stress responses like autophagy and unfolded protein response (UPR). Both autophagy and UPR are connected to programed cell death I (apoptosis) in chronic stress conditions to regulate cellular homeostasis via Bcl2 family proteins, CHOP and Beclin-1. In this review article we first briefly discuss arboviruses, influenza virus, and HIV and then describe the concepts of apoptosis, autophagy, and UPR. Finally, we focus upon how apoptosis, autophagy, and UPR are involved in the regulation of cellular responses to arboviruses, influenza virus and HIV infections.

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“…have been previously described [20]. Vero cells (ATCC, CCL-81) and HEK 293T (CRL-3216) were cultured at 37 °C under a 5% CO2 atmosphere in MEM medium (PAN Biotech, Aidenbach, Germany), supplemented with 5% heat-inactivated foetal bovine serum (FBS) (PAN Biotech, Aidenbach, Germany), A549-Dual™ cells (InvivoGen, Toulouse, France, a549d-nfis) designated hereafter as A549 cells in MEM medium supplemented with 10% heat-inactivated FBS.…”

Section: Viruses Cell Lines and Reagentsmentioning

confidence: 99%

The ZIKA Virus Controls Cell Death through the Anti-Apoptotic Bcl-2 Family Proteins

Turpin¹,

Frumence²,

Desprès³

et al. 2019

Preprint

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Zika virus (ZIKV) is an emerging human mosquito-transmitted pathogen of global concern, known to cause severe complications such as congenital defects and neurological disorders in adults. ZIKV infection is associated with cell death. However, previous studies suggest that the virally-induced apoptosis occurs at a slower rate compared to the course of viral production. In this present study, we investigated the capacity of ZIKV to delay host cell apoptosis. We provide evidence that ZIKV has the ability to control programmed cell death whether it is intrinsically or extrinsically induced. In cells expressing viral replicon-type constructions, we show that this control is achieved through replication. Finally, our work highlights an important role for anti-apoptotic Bcl-2 family protein in the ability of ZIKV to control apoptotic pathways, avoiding premature cell death and thereby promoting virus replication in the host-cell.

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The structural proteins of epidemic and historical strains of Zika virus differ in their ability to initiate viral infection in human host cells

Cited by 46 publications

References 43 publications

Zika Virus Envelope Protein Forms Disulfide Bond-dependent Polymers in Connection with a Persistent ER Stress in A549 Cells

Zika Virus Envelope Protein Forms Disulfide Bond-dependent Polymers in Connection with a Persistent ER Stress in A549 Cells

The roles of apoptosis, autophagy and unfolded protein response in arbovirus, influenza virus, and HIV infections

The ZIKA Virus Controls Cell Death through the Anti-Apoptotic Bcl-2 Family Proteins

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