Tags

Type your tag names separated by a space and hit enter

Tropism of and innate immune responses to the novel human betacoronavirus lineage C virus in human ex vivo respiratory organ cultures.
J Virol. 2013 Jun; 87(12):6604-14.JV

Abstract

Since April 2012, there have been 17 laboratory-confirmed human cases of respiratory disease associated with newly recognized human betacoronavirus lineage C virus EMC (HCoV-EMC), and 7 of them were fatal. The transmissibility and pathogenesis of HCoV-EMC remain poorly understood, and elucidating its cellular tropism in human respiratory tissues will provide mechanistic insights into the key cellular targets for virus propagation and spread. We utilized ex vivo cultures of human bronchial and lung tissue specimens to investigate the tissue tropism and virus replication kinetics following experimental infection with HCoV-EMC compared with those following infection with human coronavirus 229E (HCoV-229E) and severe acute respiratory syndrome coronavirus (SARS-CoV). The innate immune responses elicited by HCoV-EMC were also investigated. HCoV-EMC productively replicated in human bronchial and lung ex vivo organ cultures. While SARS-CoV productively replicated in lung tissue, replication in human bronchial tissue was limited. Immunohistochemistry revealed that HCoV-EMC infected nonciliated bronchial epithelium, bronchiolar epithelial cells, alveolar epithelial cells, and endothelial cells. Transmission electron microscopy showed virions within the cytoplasm of bronchial epithelial cells and budding virions from alveolar epithelial cells (type II). In contrast, there was minimal HCoV-229E infection in these tissues. HCoV-EMC failed to elicit strong type I or III interferon (IFN) or proinflammatory innate immune responses in ex vivo respiratory tissue cultures. Treatment of human lung tissue ex vivo organ cultures with type I IFNs (alpha and beta IFNs) at 1 h postinfection reduced the replication of HCoV-EMC, suggesting a potential therapeutic use of IFNs for treatment of human infection.

Authors+Show Affiliations

Centre of Influenza Research and School of Public Health, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23552422

Citation

Chan, Renee W Y., et al. "Tropism of and Innate Immune Responses to the Novel Human Betacoronavirus Lineage C Virus in Human Ex Vivo Respiratory Organ Cultures." Journal of Virology, vol. 87, no. 12, 2013, pp. 6604-14.
Chan RW, Chan MC, Agnihothram S, et al. Tropism of and innate immune responses to the novel human betacoronavirus lineage C virus in human ex vivo respiratory organ cultures. J Virol. 2013;87(12):6604-14.
Chan, R. W., Chan, M. C., Agnihothram, S., Chan, L. L., Kuok, D. I., Fong, J. H., Guan, Y., Poon, L. L., Baric, R. S., Nicholls, J. M., & Peiris, J. S. (2013). Tropism of and innate immune responses to the novel human betacoronavirus lineage C virus in human ex vivo respiratory organ cultures. Journal of Virology, 87(12), 6604-14. https://doi.org/10.1128/JVI.00009-13
Chan RW, et al. Tropism of and Innate Immune Responses to the Novel Human Betacoronavirus Lineage C Virus in Human Ex Vivo Respiratory Organ Cultures. J Virol. 2013;87(12):6604-14. PubMed PMID: 23552422.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tropism of and innate immune responses to the novel human betacoronavirus lineage C virus in human ex vivo respiratory organ cultures. AU - Chan,Renee W Y, AU - Chan,Michael C W, AU - Agnihothram,Sudhakar, AU - Chan,Louisa L Y, AU - Kuok,Denise I T, AU - Fong,Joanne H M, AU - Guan,Y, AU - Poon,Leo L M, AU - Baric,Ralph S, AU - Nicholls,John M, AU - Peiris,J S Malik, Y1 - 2013/04/03/ PY - 2013/4/5/entrez PY - 2013/4/5/pubmed PY - 2013/7/31/medline SP - 6604 EP - 14 JF - Journal of virology JO - J. Virol. VL - 87 IS - 12 N2 - Since April 2012, there have been 17 laboratory-confirmed human cases of respiratory disease associated with newly recognized human betacoronavirus lineage C virus EMC (HCoV-EMC), and 7 of them were fatal. The transmissibility and pathogenesis of HCoV-EMC remain poorly understood, and elucidating its cellular tropism in human respiratory tissues will provide mechanistic insights into the key cellular targets for virus propagation and spread. We utilized ex vivo cultures of human bronchial and lung tissue specimens to investigate the tissue tropism and virus replication kinetics following experimental infection with HCoV-EMC compared with those following infection with human coronavirus 229E (HCoV-229E) and severe acute respiratory syndrome coronavirus (SARS-CoV). The innate immune responses elicited by HCoV-EMC were also investigated. HCoV-EMC productively replicated in human bronchial and lung ex vivo organ cultures. While SARS-CoV productively replicated in lung tissue, replication in human bronchial tissue was limited. Immunohistochemistry revealed that HCoV-EMC infected nonciliated bronchial epithelium, bronchiolar epithelial cells, alveolar epithelial cells, and endothelial cells. Transmission electron microscopy showed virions within the cytoplasm of bronchial epithelial cells and budding virions from alveolar epithelial cells (type II). In contrast, there was minimal HCoV-229E infection in these tissues. HCoV-EMC failed to elicit strong type I or III interferon (IFN) or proinflammatory innate immune responses in ex vivo respiratory tissue cultures. Treatment of human lung tissue ex vivo organ cultures with type I IFNs (alpha and beta IFNs) at 1 h postinfection reduced the replication of HCoV-EMC, suggesting a potential therapeutic use of IFNs for treatment of human infection. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/23552422/Tropism_of_and_innate_immune_responses_to_the_novel_human_betacoronavirus_lineage_C_virus_in_human_ex_vivo_respiratory_organ_cultures_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=23552422 DB - PRIME DP - Unbound Medicine ER -