About: Trypsin Treatment Unlocks Barrier for Zoonotic Bat Coronavirus Infection

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

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Trypsin Treatment Unlocks Barrier for Zoonotic Bat Coronavirus Infection
Creator	Baric, Ralph Gralinski, Lisa Yount, Boyd Wang, Lingshu Scobey, Trevor Dinnon, Kenneth Anthony, Simon Menachery, Vineet Graham, Barney Graham, Rachel Hale, Andrew Lipkin, W Mcanarney, Eileen Randell, Scott
source	Medline; PMC
abstract	Traditionally, the emergence of coronaviruses (CoVs) has been attributed to a gain in receptor binding in a new host. Our previous work with severe acute respiratory syndrome (SARS)-like viruses argued that bats already harbor CoVs with the ability to infect humans without adaptation. These results suggested that additional barriers limit the emergence of zoonotic CoV. In this work, we describe overcoming host restriction of two Middle East respiratory syndrome (MERS)-like bat CoVs using exogenous protease treatment. We found that the spike protein of PDF2180-CoV, a MERS-like virus found in a Ugandan bat, could mediate infection of Vero and human cells in the presence of exogenous trypsin. We subsequently show that the bat virus spike can mediate the infection of human gut cells but is unable to infect human lung cells. Using receptor-blocking antibodies, we show that infection with the PDF2180 spike does not require MERS-CoV receptor DPP4 and antibodies developed against the MERS spike receptor-binding domain and S2 portion are ineffective in neutralizing the PDF2180 chimera. Finally, we found that the addition of exogenous trypsin also rescues HKU5-CoV, a second bat group 2c CoV. Together, these results indicate that proteolytic cleavage of the spike, not receptor binding, is the primary infection barrier for these two group 2c CoVs. Coupled with receptor binding, proteolytic activation offers a new parameter to evaluate the emergence potential of bat CoVs and offers a means to recover previously unrecoverable zoonotic CoV strains. IMPORTANCE Overall, our studies demonstrate that proteolytic cleavage is the primary barrier to infection for a subset of zoonotic coronaviruses. Moving forward, the results argue that both receptor binding and proteolytic cleavage of the spike are critical factors that must be considered for evaluating the emergence potential and risk posed by zoonotic coronaviruses. In addition, the findings also offer a novel means to recover previously uncultivable zoonotic coronavirus strains and argue that other tissues, including the digestive tract, could be a site for future coronavirus emergence events in humans.
has issue date	2020-02-14(xsd:dateTime)
bibo:doi	10.1128/jvi.01774-19
bibo:pmid	31801868
has license	no-cc
sha1sum (hex)	54f4a3d3d506617427d6c98cbc635409120988e5
schema:url	https://doi.org/10.1128/jvi.01774-19
resource representing a document's title	Trypsin Treatment Unlocks Barrier for Zoonotic Bat Coronavirus Infection
has PubMed Central identifier	PMC7022341
has PubMed identifier	31801868
schema:publication	J Virol
resource representing a document's body	covid:54f4a3d3d506617427d6c98cbc635409120988e5#body_text
is schema:about of	named entity 'exogenous' named entity 'group' named entity 'trypsin' named entity 'site' named entity 'receptor' named entity 'tissues' named entity 'spike' named entity 'primary' named entity 'exogenous' named entity 'severe acute respiratory syndrome (SARS)' named entity 'human cells' named entity 'Bat' named entity 'UGANDAN' named entity 'PROTEASE' named entity 'SPIKE PROTEIN' named entity 'ABILITY TO' named entity 'DIGESTIVE TRACT' named entity 'OFFER' named entity 'TRYPSIN' covid:arg/54f4a3d3d506617427d6c98cbc635409120988e5 named entity 'infection' named entity 'argue' named entity 'host' named entity 'spike' named entity 'spike' named entity 'coronavirus' named entity 'spike' named entity 'antibodies' named entity 'potential' named entity 'argue' named entity 'protein' named entity 'receptor' named entity 'suggested' named entity 'zoonotic' named entity 'addition' named entity 'bat' named entity 'receptor' named entity 'zoonotic' named entity 'SARS' named entity 'spike protein' named entity 'infection' named entity 'coronaviruses' named entity 'infection barrier' named entity 'viruses' named entity 'bat' named entity 'DPP4' named entity 'proteolytic cleavage' named entity 'Middle East respiratory syndrome' named entity 'exogenous' named entity 'zoonotic' named entity 'infection' named entity 'Coronavirus' named entity 'Overall' named entity 'receptor' named entity 'trypsin' named entity 'antisera' named entity 'antibodies' named entity 'wild-type' named entity 'infection' named entity 'HKU5' named entity 'enteric viruses' named entity 'RNA' named entity 'proteolytic cleavage' named entity 'infection' named entity 'porcine epidemic diarrhea virus' named entity 'bat' named entity 'primers' named entity 'wild-type'

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