About: Ca2+ ions promote fusion of Middle East Respiratory Syndrome coronavirus with host cells and increase infectivity

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About: Ca2+ ions promote fusion of Middle East Respiratory Syndrome coronavirus with host cells and increase infectivity Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Ca2+ ions promote fusion of Middle East Respiratory Syndrome coronavirus with host cells and increase infectivity
Creator	Daniel, Susan Tang, Tiffany Freed, Jack Lai, Alex Whittaker, Gary »more»
source	BioRxiv; MedRxiv
abstract	Middle East respiratory syndrome coronavirus (MERS-CoV) is a major emerging zoonotic infectious disease. Since its first outbreak in 2012, the virus has repeatedly transmitted from camels to humans with 2,468 confirmed cases, causing 851 deaths. To date, there are no efficacious drugs and vaccines against MERS-CoV, increasing its potential to cause a public health emergency. A critical step in the life cycle of MERS-CoV is the fusion with the host cell with its spike (S) protein as main determinant of viral entry. Proteolytic cleavage of S exposes its fusion peptide (FP), which initiates membrane fusion. Previous studies on the related severe acute respiratory syndrome coronavirus (SARS-CoV) FP have shown that calcium (Ca2+) plays an important role for fusogenic activity via a Ca2+ binding pocket with conserved glutamic acid (E) and aspartic acid (D) residues. SARS-CoV and MERS-CoV FP share a high sequence homology and here, we investigated whether Ca2+ is required for MERS-CoV fusion by substituting E and D residues in the MERS-CoV FP with neutrally charged alanines. Upon verifying mutant cell surface expression and proteolytic cleavage, we tested the mutants ability to mediate infection of pseudo-particles (PPs) on host cells without and with Ca2+. Our results demonstrate that intracellular Ca2+ enhances MERS-CoV WT PPs infection by approximately two-fold and that E891 is a crucial residue for Ca2+ interaction. Electron spin resonance revealed that this enhancement could be attributed to Ca2+ increasing MERS-CoV FP fusion-relevant membrane ordering. Intriguingly, isothermal calorimetry titration showed that MERS-CoV FP binds one Ca2+, as opposed to SARS-CoV FP which binds two. Our data suggests that there are significant differences in FP-Ca2+ interactions of MERS-CoV and SARS-CoV FP despite their high sequence similarity and that the number of Ca2+ ions interacting with the FP has implications on the fusion dynamics of the virus.
has issue date	2019-12-19(xsd:dateTime)
bibo:doi	10.1101/2019.12.18.881391
has license	biorxiv
sha1sum (hex)	edf299be9be6a5616274c1c68448b880758b52f8
schema:url	https://doi.org/10.1101/2019.12.18.881391
resource representing a document's title	Ca2+ ions promote fusion of Middle East Respiratory Syndrome coronavirus with host cells and increase infectivity
schema:publication	bioRxiv
resource representing a document's body	covid:edf299be9be6a5616274c1c68448b880758b52f8#body_text
is schema:about of	named entity 'host' named entity 'infectivity' named entity 'CAUSING' named entity 'LIFE CYCLE' named entity 'DETERMINANT' »more»

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