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Article: Natural Transmission of Bat-like Severe Acute Respiratory Syndrome Coronavirus 2 Without Proline-Arginine-Arginine-Alanine Variants in Coronavirus Disease 2019 Patients

TitleNatural Transmission of Bat-like Severe Acute Respiratory Syndrome Coronavirus 2 Without Proline-Arginine-Arginine-Alanine Variants in Coronavirus Disease 2019 Patients
Authors
KeywordsCOVID-19
SARS-CoV-2
Viral variants
Transmission
Furin cleavage PRRA motif
Issue Date2021
PublisherOxford University Press. The Journal's web site is located at http://www.oxfordjournals.org/our_journals/cid/
Citation
Clinical Infectious Diseases, 2021, v. 73 n. 2, p. e437-e444 How to Cite?
AbstractBackground: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains the furin cleavage Proline-Arginine-Arginine-Alanine (PRRA) motif in the S1/S2 region, which enhances viral pathogenicity but is absent in closely related bat and pangolin coronaviruses. Whether bat-like coronaviral variants without PRRA (∆PRRA) can establish natural infections in humans is unknown. Methods; Here, we developed a duplex digital polymerase chain reaction assay to examine ∆PRRA variants in Vero-E6-propagated isolates, human organoids, experimentally infected hamsters, and coronavirus disease 2019 (COVID-19) patients. Results: We found that SARS-CoV-2, as currently transmitting in humans, contained a quasispecies of wild-type, ∆PRRA variants and variants that have mutations upstream of the PRRA motif. Moreover, the ∆PRRA variants were readily detected despite being at a low intra-host frequency in transmitted founder viruses in hamsters and in COVID-19 patients, including in acute cases and a family cluster, with a prevalence rate of 52.9%. Conclusions: Our findings demonstrate that bat-like SARS-CoV-2ΔPRRA not only naturally exists but remains transmissible in COVID-19 patients, which has significant implications regarding the zoonotic origin and natural evolution of SARS-CoV-2.
Persistent Identifierhttp://hdl.handle.net/10722/289790
ISSN
2023 Impact Factor: 8.2
2023 SCImago Journal Rankings: 3.308
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWong, YC-
dc.contributor.authorLau, SY-
dc.contributor.authorTo, KKW-
dc.contributor.authorMok, BWY-
dc.contributor.authorLi, X-
dc.contributor.authorWang, P-
dc.contributor.authorDeng, S-
dc.contributor.authorWoo, KF-
dc.contributor.authorDu, Z-
dc.contributor.authorLi, C-
dc.contributor.authorZhou, J-
dc.contributor.authorChan, JFW-
dc.contributor.authorYuen, KY-
dc.contributor.authorChen, H-
dc.contributor.authorChen, Z-
dc.date.accessioned2020-10-22T08:17:31Z-
dc.date.available2020-10-22T08:17:31Z-
dc.date.issued2021-
dc.identifier.citationClinical Infectious Diseases, 2021, v. 73 n. 2, p. e437-e444-
dc.identifier.issn1058-4838-
dc.identifier.urihttp://hdl.handle.net/10722/289790-
dc.description.abstractBackground: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contains the furin cleavage Proline-Arginine-Arginine-Alanine (PRRA) motif in the S1/S2 region, which enhances viral pathogenicity but is absent in closely related bat and pangolin coronaviruses. Whether bat-like coronaviral variants without PRRA (∆PRRA) can establish natural infections in humans is unknown. Methods; Here, we developed a duplex digital polymerase chain reaction assay to examine ∆PRRA variants in Vero-E6-propagated isolates, human organoids, experimentally infected hamsters, and coronavirus disease 2019 (COVID-19) patients. Results: We found that SARS-CoV-2, as currently transmitting in humans, contained a quasispecies of wild-type, ∆PRRA variants and variants that have mutations upstream of the PRRA motif. Moreover, the ∆PRRA variants were readily detected despite being at a low intra-host frequency in transmitted founder viruses in hamsters and in COVID-19 patients, including in acute cases and a family cluster, with a prevalence rate of 52.9%. Conclusions: Our findings demonstrate that bat-like SARS-CoV-2ΔPRRA not only naturally exists but remains transmissible in COVID-19 patients, which has significant implications regarding the zoonotic origin and natural evolution of SARS-CoV-2.-
dc.languageeng-
dc.publisherOxford University Press. The Journal's web site is located at http://www.oxfordjournals.org/our_journals/cid/-
dc.relation.ispartofClinical Infectious Diseases-
dc.subjectCOVID-19-
dc.subjectSARS-CoV-2-
dc.subjectViral variants-
dc.subjectTransmission-
dc.subjectFurin cleavage PRRA motif-
dc.titleNatural Transmission of Bat-like Severe Acute Respiratory Syndrome Coronavirus 2 Without Proline-Arginine-Arginine-Alanine Variants in Coronavirus Disease 2019 Patients-
dc.typeArticle-
dc.identifier.emailLau, SY: sylau926@hkucc.hku.hk-
dc.identifier.emailTo, KKW: kelvinto@hku.hk-
dc.identifier.emailMok, BWY: bobomok@hku.hk-
dc.identifier.emailWang, P: puiwang@hkucc.hku.hk-
dc.identifier.emailDu, Z: duzl@hku.hk-
dc.identifier.emailLi, C: licun@hku.hk-
dc.identifier.emailZhou, J: jiezhou@hku.hk-
dc.identifier.emailChan, JFW: jfwchan@hku.hk-
dc.identifier.emailYuen, KY: kyyuen@hkucc.hku.hk-
dc.identifier.emailChen, H: hlchen@hku.hk-
dc.identifier.emailChen, Z: zchenai@hku.hk-
dc.identifier.authorityTo, KKW=rp01384-
dc.identifier.authorityLi, C=rp02783-
dc.identifier.authorityZhou, J=rp01412-
dc.identifier.authorityChan, JFW=rp01736-
dc.identifier.authorityYuen, KY=rp00366-
dc.identifier.authorityChen, H=rp00383-
dc.identifier.authorityChen, Z=rp00243-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1093/cid/ciaa953-
dc.identifier.pmid32649739-
dc.identifier.pmcidPMC7454488-
dc.identifier.scopuseid_2-s2.0-85112124874-
dc.identifier.hkuros317226-
dc.identifier.volume73-
dc.identifier.issue2-
dc.identifier.spagee437-
dc.identifier.epagee444-
dc.identifier.isiWOS:000697378800027-
dc.publisher.placeUnited States-
dc.identifier.issnl1058-4838-

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