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Replication of MERS and SARS coronaviruses in bat cells offers insights to their ancestral origins.
Emerg Microbes Infect. 2018 Dec 10; 7(1):209.EM

Abstract

Previous findings of Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses in bats, and the ability of Tylonycteris-BatCoV HKU4 spike protein to utilize MERS-CoV receptor, human dipeptidyl peptidase 4 hDPP4, suggest a bat ancestral origin of MERS-CoV. We developed 12 primary bat cell lines from seven bat species, including Tylonycteris pachypus, Pipistrellus abramus and Rhinolophus sinicus (hosts of Tylonycteris-BatCoV HKU4, Pipistrellus-BatCoV HKU5, and SARS-related-CoV respectively), and tested their susceptibilities to MERS-CoVs, SARS-CoV, and human coronavirus 229E (HCoV-229E). Five cell lines, including P. abramus and R. sinicus but not T. pachypus cells, were susceptible to human MERS-CoV EMC/2012. However, three tested camel MERS-CoV strains showed different infectivities, with only two strains capable of infecting three and one cell lines respectively. SARS-CoV can only replicate in R. sinicus cells, while HCoV-229E cannot replicate in any bat cells. Bat dipeptidyl peptidase 4 (DPP4) sequences were closely related to those of human and non-human primates but distinct from dromedary DPP4 sequence. Critical residues for binding to MERS-CoV spike protein were mostly conserved in bat DPP4. DPP4 was expressed in the five bat cells susceptible to MERS-CoV, with significantly higher mRNA expression levels than those in non-susceptible cells (P = 0.0174), supporting that DPP4 expression is critical for MERS-CoV infection in bats. However, overexpression of T. pachypus DPP4 failed to confer MERS-CoV susceptibility in T. pachypus cells, suggesting other cellular factors in determining viral replication. The broad cellular tropism of MERS-CoV should prompt further exploration of host diversity of related viruses to identify its ancestral origin.

Authors+Show Affiliations

State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. skplau@hku.hk. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. skplau@hku.hk. Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. skplau@hku.hk. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. skplau@hku.hk.Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.Central Veterinary Research Laboratory, Dubai, United Arab Emirates.State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.State Key Laboratory of Emerging Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. pcywoo@hku.hk. Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. pcywoo@hku.hk. Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. pcywoo@hku.hk. Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China. pcywoo@hku.hk.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30531999

Citation

Lau, Susanna K P., et al. "Replication of MERS and SARS Coronaviruses in Bat Cells Offers Insights to Their Ancestral Origins." Emerging Microbes & Infections, vol. 7, no. 1, 2018, p. 209.
Lau SKP, Fan RYY, Luk HKH, et al. Replication of MERS and SARS coronaviruses in bat cells offers insights to their ancestral origins. Emerg Microbes Infect. 2018;7(1):209.
Lau, S. K. P., Fan, R. Y. Y., Luk, H. K. H., Zhu, L., Fung, J., Li, K. S. M., Wong, E. Y. M., Ahmed, S. S., Chan, J. F. W., Kok, R. K. H., Chan, K. H., Wernery, U., Yuen, K. Y., & Woo, P. C. Y. (2018). Replication of MERS and SARS coronaviruses in bat cells offers insights to their ancestral origins. Emerging Microbes & Infections, 7(1), 209. https://doi.org/10.1038/s41426-018-0208-9
Lau SKP, et al. Replication of MERS and SARS Coronaviruses in Bat Cells Offers Insights to Their Ancestral Origins. Emerg Microbes Infect. 2018 Dec 10;7(1):209. PubMed PMID: 30531999.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Replication of MERS and SARS coronaviruses in bat cells offers insights to their ancestral origins. AU - Lau,Susanna K P, AU - Fan,Rachel Y Y, AU - Luk,Hayes K H, AU - Zhu,Longchao, AU - Fung,Joshua, AU - Li,Kenneth S M, AU - Wong,Emily Y M, AU - Ahmed,Syed Shakeel, AU - Chan,Jasper F W, AU - Kok,Raven K H, AU - Chan,Kwok-Hung, AU - Wernery,Ulrich, AU - Yuen,Kwok-Yung, AU - Woo,Patrick C Y, Y1 - 2018/12/10/ PY - 2018/08/24/received PY - 2018/11/11/accepted PY - 2018/11/08/revised PY - 2018/12/12/entrez PY - 2018/12/12/pubmed PY - 2019/4/23/medline SP - 209 EP - 209 JF - Emerging microbes & infections JO - Emerg Microbes Infect VL - 7 IS - 1 N2 - Previous findings of Middle East Respiratory Syndrome coronavirus (MERS-CoV)-related viruses in bats, and the ability of Tylonycteris-BatCoV HKU4 spike protein to utilize MERS-CoV receptor, human dipeptidyl peptidase 4 hDPP4, suggest a bat ancestral origin of MERS-CoV. We developed 12 primary bat cell lines from seven bat species, including Tylonycteris pachypus, Pipistrellus abramus and Rhinolophus sinicus (hosts of Tylonycteris-BatCoV HKU4, Pipistrellus-BatCoV HKU5, and SARS-related-CoV respectively), and tested their susceptibilities to MERS-CoVs, SARS-CoV, and human coronavirus 229E (HCoV-229E). Five cell lines, including P. abramus and R. sinicus but not T. pachypus cells, were susceptible to human MERS-CoV EMC/2012. However, three tested camel MERS-CoV strains showed different infectivities, with only two strains capable of infecting three and one cell lines respectively. SARS-CoV can only replicate in R. sinicus cells, while HCoV-229E cannot replicate in any bat cells. Bat dipeptidyl peptidase 4 (DPP4) sequences were closely related to those of human and non-human primates but distinct from dromedary DPP4 sequence. Critical residues for binding to MERS-CoV spike protein were mostly conserved in bat DPP4. DPP4 was expressed in the five bat cells susceptible to MERS-CoV, with significantly higher mRNA expression levels than those in non-susceptible cells (P = 0.0174), supporting that DPP4 expression is critical for MERS-CoV infection in bats. However, overexpression of T. pachypus DPP4 failed to confer MERS-CoV susceptibility in T. pachypus cells, suggesting other cellular factors in determining viral replication. The broad cellular tropism of MERS-CoV should prompt further exploration of host diversity of related viruses to identify its ancestral origin. SN - 2222-1751 UR - https://www.unboundmedicine.com/medline/citation/30531999/Replication_of_MERS_and_SARS_coronaviruses_in_bat_cells_offers_insights_to_their_ancestral_origins_ L2 - https://www.tandfonline.com/doi/full/10.1038/s41426-018-0208-9 DB - PRIME DP - Unbound Medicine ER -