Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus

ABSTRACT The evolutionary origins of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) are unknown. Current evidence suggests that insectivorous bats are likely to be the original source, as several 2c CoVs have been described from various species in the family Vespertilionidae. Here, w...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	S. J. Anthony, K. Gilardi, V. D. Menachery, T. Goldstein, B. Ssebide, R. Mbabazi, I. Navarrete-Macias, E. Liang, H. Wells, A. Hicks, A. Petrosov, D. K. Byarugaba, K. Debbink, K. H. Dinnon, T. Scobey, S. H. Randell, B. L. Yount, M. Cranfield, C. K. Johnson, R. S. Baric, W. I. Lipkin, J. A. K. Mazet
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	bat MERS coronavirus spike Uganda zoonoses Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/931f35c9c32a4ca38e5bc6819a478d09
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:931f35c9c32a4ca38e5bc6819a478d09
record_format	dspace
spelling	oai:doaj.org-article:931f35c9c32a4ca38e5bc6819a478d092021-11-15T15:50:59ZFurther Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus10.1128/mBio.00373-172150-7511https://doaj.org/article/931f35c9c32a4ca38e5bc6819a478d092017-05-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00373-17https://doaj.org/toc/2150-7511ABSTRACT The evolutionary origins of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) are unknown. Current evidence suggests that insectivorous bats are likely to be the original source, as several 2c CoVs have been described from various species in the family Vespertilionidae. Here, we describe a MERS-like CoV identified from a Pipistrellus cf. hesperidus bat sampled in Uganda (strain PREDICT/PDF-2180), further supporting the hypothesis that bats are the evolutionary source of MERS-CoV. Phylogenetic analysis showed that PREDICT/PDF-2180 is closely related to MERS-CoV across much of its genome, consistent with a common ancestry; however, the spike protein was highly divergent (46% amino acid identity), suggesting that the two viruses may have different receptor binding properties. Indeed, several amino acid substitutions were identified in key binding residues that were predicted to block PREDICT/PDF-2180 from attaching to the MERS-CoV DPP4 receptor. To experimentally test this hypothesis, an infectious MERS-CoV clone expressing the PREDICT/PDF-2180 spike protein was generated. Recombinant viruses derived from the clone were replication competent but unable to spread and establish new infections in Vero cells or primary human airway epithelial cells. Our findings suggest that PREDICT/PDF-2180 is unlikely to pose a zoonotic threat. Recombination in the S1 subunit of the spike gene was identified as the primary mechanism driving variation in the spike phenotype and was likely one of the critical steps in the evolution and emergence of MERS-CoV in humans. IMPORTANCE Global surveillance efforts for undiscovered viruses are an important component of pandemic prevention initiatives. These surveys can be useful for finding novel viruses and for gaining insights into the ecological and evolutionary factors driving viral diversity; however, finding a viral sequence is not sufficient to determine whether it can infect people (i.e., poses a zoonotic threat). Here, we investigated the specific zoonotic risk of a MERS-like coronavirus (PREDICT/PDF-2180) identified in a bat from Uganda and showed that, despite being closely related to MERS-CoV, it is unlikely to pose a threat to humans. We suggest that this approach constitutes an appropriate strategy for beginning to determine the zoonotic potential of wildlife viruses. By showing that PREDICT/PDF-2180 does not infect cells that express the functional receptor for MERS-CoV, we further show that recombination was likely to be the critical step that allowed MERS to emerge in humans.S. J. AnthonyK. GilardiV. D. MenacheryT. GoldsteinB. SsebideR. MbabaziI. Navarrete-MaciasE. LiangH. WellsA. HicksA. PetrosovD. K. ByarugabaK. DebbinkK. H. DinnonT. ScobeyS. H. RandellB. L. YountM. CranfieldC. K. JohnsonR. S. BaricW. I. LipkinJ. A. K. MazetAmerican Society for MicrobiologyarticlebatMERS coronavirusspikeUgandazoonosesMicrobiologyQR1-502ENmBio, Vol 8, Iss 2 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	bat MERS coronavirus spike Uganda zoonoses Microbiology QR1-502
spellingShingle	bat MERS coronavirus spike Uganda zoonoses Microbiology QR1-502 S. J. Anthony K. Gilardi V. D. Menachery T. Goldstein B. Ssebide R. Mbabazi I. Navarrete-Macias E. Liang H. Wells A. Hicks A. Petrosov D. K. Byarugaba K. Debbink K. H. Dinnon T. Scobey S. H. Randell B. L. Yount M. Cranfield C. K. Johnson R. S. Baric W. I. Lipkin J. A. K. Mazet Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus
description	ABSTRACT The evolutionary origins of Middle East respiratory syndrome (MERS) coronavirus (MERS-CoV) are unknown. Current evidence suggests that insectivorous bats are likely to be the original source, as several 2c CoVs have been described from various species in the family Vespertilionidae. Here, we describe a MERS-like CoV identified from a Pipistrellus cf. hesperidus bat sampled in Uganda (strain PREDICT/PDF-2180), further supporting the hypothesis that bats are the evolutionary source of MERS-CoV. Phylogenetic analysis showed that PREDICT/PDF-2180 is closely related to MERS-CoV across much of its genome, consistent with a common ancestry; however, the spike protein was highly divergent (46% amino acid identity), suggesting that the two viruses may have different receptor binding properties. Indeed, several amino acid substitutions were identified in key binding residues that were predicted to block PREDICT/PDF-2180 from attaching to the MERS-CoV DPP4 receptor. To experimentally test this hypothesis, an infectious MERS-CoV clone expressing the PREDICT/PDF-2180 spike protein was generated. Recombinant viruses derived from the clone were replication competent but unable to spread and establish new infections in Vero cells or primary human airway epithelial cells. Our findings suggest that PREDICT/PDF-2180 is unlikely to pose a zoonotic threat. Recombination in the S1 subunit of the spike gene was identified as the primary mechanism driving variation in the spike phenotype and was likely one of the critical steps in the evolution and emergence of MERS-CoV in humans. IMPORTANCE Global surveillance efforts for undiscovered viruses are an important component of pandemic prevention initiatives. These surveys can be useful for finding novel viruses and for gaining insights into the ecological and evolutionary factors driving viral diversity; however, finding a viral sequence is not sufficient to determine whether it can infect people (i.e., poses a zoonotic threat). Here, we investigated the specific zoonotic risk of a MERS-like coronavirus (PREDICT/PDF-2180) identified in a bat from Uganda and showed that, despite being closely related to MERS-CoV, it is unlikely to pose a threat to humans. We suggest that this approach constitutes an appropriate strategy for beginning to determine the zoonotic potential of wildlife viruses. By showing that PREDICT/PDF-2180 does not infect cells that express the functional receptor for MERS-CoV, we further show that recombination was likely to be the critical step that allowed MERS to emerge in humans.
format	article
author	S. J. Anthony K. Gilardi V. D. Menachery T. Goldstein B. Ssebide R. Mbabazi I. Navarrete-Macias E. Liang H. Wells A. Hicks A. Petrosov D. K. Byarugaba K. Debbink K. H. Dinnon T. Scobey S. H. Randell B. L. Yount M. Cranfield C. K. Johnson R. S. Baric W. I. Lipkin J. A. K. Mazet
author_facet	S. J. Anthony K. Gilardi V. D. Menachery T. Goldstein B. Ssebide R. Mbabazi I. Navarrete-Macias E. Liang H. Wells A. Hicks A. Petrosov D. K. Byarugaba K. Debbink K. H. Dinnon T. Scobey S. H. Randell B. L. Yount M. Cranfield C. K. Johnson R. S. Baric W. I. Lipkin J. A. K. Mazet
author_sort	S. J. Anthony
title	Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus
title_short	Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus
title_full	Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus
title_fullStr	Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus
title_full_unstemmed	Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus
title_sort	further evidence for bats as the evolutionary source of middle east respiratory syndrome coronavirus
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/931f35c9c32a4ca38e5bc6819a478d09
work_keys_str_mv	AT sjanthony furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus AT kgilardi furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus AT vdmenachery furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus AT tgoldstein furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus AT bssebide furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus AT rmbabazi furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus AT inavarretemacias furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus AT eliang furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus AT hwells furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus AT ahicks furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus AT apetrosov furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus AT dkbyarugaba furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus AT kdebbink furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus AT khdinnon furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus AT tscobey furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus AT shrandell furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus AT blyount furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus AT mcranfield furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus AT ckjohnson furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus AT rsbaric furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus AT wilipkin furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus AT jakmazet furtherevidenceforbatsastheevolutionarysourceofmiddleeastrespiratorysyndromecoronavirus
_version_	1718427413616001024

Further Evidence for Bats as the Evolutionary Source of Middle East Respiratory Syndrome Coronavirus

Ejemplares similares