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Cell host response to infection with novel human coronavirus EMC predicts potential antivirals and important differences with SARS coronavirus.
mBio. 2013 Apr 30; 4(3):e00165-13.MBIO

Abstract

A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as the causative agent of a severe acute respiratory syndrome (SARS) resembling the illness caused by SARS coronavirus (SARS-CoV). Although derived from the CoV family, the two viruses are genetically distinct and do not use the same receptor. Here, we investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. HCoV-EMC was able to replicate as efficiently as SARS-CoV in Calu-3 cells and similarly induced minimal transcriptomic changes before 12 h postinfection. Later in infection, HCoV-EMC induced a massive dysregulation of the host transcriptome, to a much greater extent than SARS-CoV. Both viruses induced a similar activation of pattern recognition receptors and the interleukin 17 (IL-17) pathway, but HCoV-EMC specifically down-regulated the expression of several genes within the antigen presentation pathway, including both type I and II major histocompatibility complex (MHC) genes. This could have an important impact on the ability of the host to mount an adaptive host response. A unique set of 207 genes was dysregulated early and permanently throughout infection with HCoV-EMC, and was used in a computational screen to predict potential antiviral compounds, including kinase inhibitors and glucocorticoids. Overall, HCoV-EMC and SARS-CoV elicit distinct host gene expression responses, which might impact in vivo pathogenesis and could orient therapeutic strategies against that emergent virus.

IMPORTANCE

Identification of a novel coronavirus causing fatal respiratory infection in humans raises concerns about a possible widespread outbreak of severe respiratory infection similar to the one caused by SARS-CoV. Using a human lung epithelial cell line and global transcriptomic profiling, we identified differences in the host response between HCoV-EMC and SARS-CoV. This enables rapid assessment of viral properties and the ability to anticipate possible differences in human clinical responses to HCoV-EMC and SARS-CoV. We used this information to predict potential effective drugs against HCoV-EMC, a method that could be more generally used to identify candidate therapeutics in future disease outbreaks. These data will help to generate hypotheses and make rapid advancements in characterizing this new virus.

Authors+Show Affiliations

Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington, USA.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 available

Pub Type(s)

Comparative Study
Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

23631916

Citation

Josset, Laurence, et al. "Cell Host Response to Infection With Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences With SARS Coronavirus." MBio, vol. 4, no. 3, 2013, pp. e00165-13.
Josset L, Menachery VD, Gralinski LE, et al. Cell host response to infection with novel human coronavirus EMC predicts potential antivirals and important differences with SARS coronavirus. mBio. 2013;4(3):e00165-13.
Josset, L., Menachery, V. D., Gralinski, L. E., Agnihothram, S., Sova, P., Carter, V. S., Yount, B. L., Graham, R. L., Baric, R. S., & Katze, M. G. (2013). Cell host response to infection with novel human coronavirus EMC predicts potential antivirals and important differences with SARS coronavirus. MBio, 4(3), e00165-13. https://doi.org/10.1128/mBio.00165-13
Josset L, et al. Cell Host Response to Infection With Novel Human Coronavirus EMC Predicts Potential Antivirals and Important Differences With SARS Coronavirus. mBio. 2013 Apr 30;4(3):e00165-13. PubMed PMID: 23631916.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cell host response to infection with novel human coronavirus EMC predicts potential antivirals and important differences with SARS coronavirus. AU - Josset,Laurence, AU - Menachery,Vineet D, AU - Gralinski,Lisa E, AU - Agnihothram,Sudhakar, AU - Sova,Pavel, AU - Carter,Victoria S, AU - Yount,Boyd L, AU - Graham,Rachel L, AU - Baric,Ralph S, AU - Katze,Michael G, Y1 - 2013/04/30/ PY - 2013/5/2/entrez PY - 2013/5/2/pubmed PY - 2013/12/16/medline SP - e00165 EP - 13 JF - mBio JO - mBio VL - 4 IS - 3 N2 - UNLABELLED: A novel human coronavirus (HCoV-EMC) was recently identified in the Middle East as the causative agent of a severe acute respiratory syndrome (SARS) resembling the illness caused by SARS coronavirus (SARS-CoV). Although derived from the CoV family, the two viruses are genetically distinct and do not use the same receptor. Here, we investigated whether HCoV-EMC and SARS-CoV induce similar or distinct host responses after infection of a human lung epithelial cell line. HCoV-EMC was able to replicate as efficiently as SARS-CoV in Calu-3 cells and similarly induced minimal transcriptomic changes before 12 h postinfection. Later in infection, HCoV-EMC induced a massive dysregulation of the host transcriptome, to a much greater extent than SARS-CoV. Both viruses induced a similar activation of pattern recognition receptors and the interleukin 17 (IL-17) pathway, but HCoV-EMC specifically down-regulated the expression of several genes within the antigen presentation pathway, including both type I and II major histocompatibility complex (MHC) genes. This could have an important impact on the ability of the host to mount an adaptive host response. A unique set of 207 genes was dysregulated early and permanently throughout infection with HCoV-EMC, and was used in a computational screen to predict potential antiviral compounds, including kinase inhibitors and glucocorticoids. Overall, HCoV-EMC and SARS-CoV elicit distinct host gene expression responses, which might impact in vivo pathogenesis and could orient therapeutic strategies against that emergent virus. IMPORTANCE: Identification of a novel coronavirus causing fatal respiratory infection in humans raises concerns about a possible widespread outbreak of severe respiratory infection similar to the one caused by SARS-CoV. Using a human lung epithelial cell line and global transcriptomic profiling, we identified differences in the host response between HCoV-EMC and SARS-CoV. This enables rapid assessment of viral properties and the ability to anticipate possible differences in human clinical responses to HCoV-EMC and SARS-CoV. We used this information to predict potential effective drugs against HCoV-EMC, a method that could be more generally used to identify candidate therapeutics in future disease outbreaks. These data will help to generate hypotheses and make rapid advancements in characterizing this new virus. SN - 2150-7511 UR - https://www.unboundmedicine.com/medline/citation/23631916/Cell_host_response_to_infection_with_novel_human_coronavirus_EMC_predicts_potential_antivirals_and_important_differences_with_SARS_coronavirus_ L2 - http://mbio.asm.org/cgi/pmidlookup?view=long&pmid=23631916 DB - PRIME DP - Unbound Medicine ER -