Host cell entry of Middle East respiratory syndrome coronavirus after two-step, furin-mediated activation of the spike protein

Proceedings of the National Academy of Sciences of the United States of America - Tập 111 Số 42 - Trang 15214-15219 - 2014
Jean K. Millet1, Gary R. Whittaker1
1Department of Microbiology and Immunology, Cornell University, Ithaca, NY 14853;

Tóm tắt

Significance The emergence of Middle East respiratory syndrome coronavirus (MERS-CoV), a deadly human coronavirus, has triggered considerable interest in the biomedical community. Similar to other enveloped viruses, coronaviruses access host cells by membrane fusion, a process mediated by specific fusion or “spike” proteins on the virion, often activated by cellular proteases. We have identified unique features of the MERS-CoV spike (S) protein cleavage activation. Our findings suggest that S can be activated by furin, a broadly expressed protease, by a two-step cleavage mechanism, occurring at distinct sites, with cleavage events temporally separated. Such furin-mediated activation is unusual in that it occurs in part during virus entry. Our findings may explain the polytropic nature, pathogenicity, and life cycle of this zoonotic coronavirus.

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Proceedings of the National Academy of Sciences of the United States of America

Tập 111 Số 42

15214-15219

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