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The spike protein of the emerging betacoronavirus EMC uses a novel coronavirus receptor for entry, can be activated by TMPRSS2, and is targeted by neutralizing antibodies.
J Virol. 2013 May; 87(10):5502-11.JV

Abstract

The novel human coronavirus EMC (hCoV-EMC), which recently emerged in Saudi Arabia, is highly pathogenic and could pose a significant threat to public health. The elucidation of hCoV-EMC interactions with host cells is critical to our understanding of the pathogenesis of this virus and to the identification of targets for antiviral intervention. Here we investigated the viral and cellular determinants governing hCoV-EMC entry into host cells. We found that the spike protein of hCoV-EMC (EMC-S) is incorporated into lentiviral particles and mediates transduction of human cell lines derived from different organs, including the lungs, kidneys, and colon, as well as primary human macrophages. Expression of the known coronavirus receptors ACE2, CD13, and CEACAM1 did not facilitate EMC-S-driven transduction, suggesting that hCoV-EMC uses a novel receptor for entry. Directed protease expression and inhibition analyses revealed that TMPRSS2 and endosomal cathepsins activate EMC-S for virus-cell fusion and constitute potential targets for antiviral intervention. Finally, EMC-S-driven transduction was abrogated by serum from an hCoV-EMC-infected patient, indicating that EMC-S-specific neutralizing antibodies can be generated in patients. Collectively, our results indicate that hCoV-EMC uses a novel receptor for protease-activated entry into human cells and might be capable of extrapulmonary spread. In addition, they define TMPRSS2 and cathepsins B and L as potential targets for intervention and suggest that neutralizing antibodies contribute to the control of hCoV-EMC infection.

Authors+Show Affiliations

Infection Biology Unit, German Primate Center, Göttingen, Germany.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 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

23468491

Citation

Gierer, Stefanie, et al. "The Spike Protein of the Emerging Betacoronavirus EMC Uses a Novel Coronavirus Receptor for Entry, Can Be Activated By TMPRSS2, and Is Targeted By Neutralizing Antibodies." Journal of Virology, vol. 87, no. 10, 2013, pp. 5502-11.
Gierer S, Bertram S, Kaup F, et al. The spike protein of the emerging betacoronavirus EMC uses a novel coronavirus receptor for entry, can be activated by TMPRSS2, and is targeted by neutralizing antibodies. J Virol. 2013;87(10):5502-11.
Gierer, S., Bertram, S., Kaup, F., Wrensch, F., Heurich, A., Krämer-Kühl, A., Welsch, K., Winkler, M., Meyer, B., Drosten, C., Dittmer, U., von Hahn, T., Simmons, G., Hofmann, H., & Pöhlmann, S. (2013). The spike protein of the emerging betacoronavirus EMC uses a novel coronavirus receptor for entry, can be activated by TMPRSS2, and is targeted by neutralizing antibodies. Journal of Virology, 87(10), 5502-11. https://doi.org/10.1128/JVI.00128-13
Gierer S, et al. The Spike Protein of the Emerging Betacoronavirus EMC Uses a Novel Coronavirus Receptor for Entry, Can Be Activated By TMPRSS2, and Is Targeted By Neutralizing Antibodies. J Virol. 2013;87(10):5502-11. PubMed PMID: 23468491.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The spike protein of the emerging betacoronavirus EMC uses a novel coronavirus receptor for entry, can be activated by TMPRSS2, and is targeted by neutralizing antibodies. AU - Gierer,Stefanie, AU - Bertram,Stephanie, AU - Kaup,Franziska, AU - Wrensch,Florian, AU - Heurich,Adeline, AU - Krämer-Kühl,Annika, AU - Welsch,Kathrin, AU - Winkler,Michael, AU - Meyer,Benjamin, AU - Drosten,Christian, AU - Dittmer,Ulf, AU - von Hahn,Thomas, AU - Simmons,Graham, AU - Hofmann,Heike, AU - Pöhlmann,Stefan, Y1 - 2013/03/06/ PY - 2013/3/8/entrez PY - 2013/3/8/pubmed PY - 2013/6/25/medline SP - 5502 EP - 11 JF - Journal of virology JO - J. Virol. VL - 87 IS - 10 N2 - The novel human coronavirus EMC (hCoV-EMC), which recently emerged in Saudi Arabia, is highly pathogenic and could pose a significant threat to public health. The elucidation of hCoV-EMC interactions with host cells is critical to our understanding of the pathogenesis of this virus and to the identification of targets for antiviral intervention. Here we investigated the viral and cellular determinants governing hCoV-EMC entry into host cells. We found that the spike protein of hCoV-EMC (EMC-S) is incorporated into lentiviral particles and mediates transduction of human cell lines derived from different organs, including the lungs, kidneys, and colon, as well as primary human macrophages. Expression of the known coronavirus receptors ACE2, CD13, and CEACAM1 did not facilitate EMC-S-driven transduction, suggesting that hCoV-EMC uses a novel receptor for entry. Directed protease expression and inhibition analyses revealed that TMPRSS2 and endosomal cathepsins activate EMC-S for virus-cell fusion and constitute potential targets for antiviral intervention. Finally, EMC-S-driven transduction was abrogated by serum from an hCoV-EMC-infected patient, indicating that EMC-S-specific neutralizing antibodies can be generated in patients. Collectively, our results indicate that hCoV-EMC uses a novel receptor for protease-activated entry into human cells and might be capable of extrapulmonary spread. In addition, they define TMPRSS2 and cathepsins B and L as potential targets for intervention and suggest that neutralizing antibodies contribute to the control of hCoV-EMC infection. SN - 1098-5514 UR - https://www.unboundmedicine.com/medline/citation/23468491/The_spike_protein_of_the_emerging_betacoronavirus_EMC_uses_a_novel_coronavirus_receptor_for_entry_can_be_activated_by_TMPRSS2_and_is_targeted_by_neutralizing_antibodies_ L2 - http://jvi.asm.org/cgi/pmidlookup?view=long&pmid=23468491 DB - PRIME DP - Unbound Medicine ER -