Two Mutations Were Critical for Bat-to-Human Transmission of Middle East Respiratory Syndrome Coronavirus

Yang Yang; Chang Liu; Lanying Du; Shibo Jiang; Zhengli Shi; Ralph S Baric; Fang Li

doi:10.1128/JVI.01279-15

Two Mutations Were Critical for Bat-to-Human Transmission of Middle East Respiratory Syndrome Coronavirus

J Virol. 2015 Sep;89(17):9119-23. doi: 10.1128/JVI.01279-15. Epub 2015 Jun 10.

Authors

Yang Yang¹, Chang Liu¹, Lanying Du², Shibo Jiang³, Zhengli Shi⁴, Ralph S Baric⁵, Fang Li⁶

Affiliations

¹ Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
² Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA.
³ Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai, China.
⁴ Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
⁵ Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
⁶ Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota, USA lifang@umn.edu.

Abstract

To understand how Middle East respiratory syndrome coronavirus (MERS-CoV) transmitted from bats to humans, we compared the virus surface spikes of MERS-CoV and a related bat coronavirus, HKU4. Although HKU4 spike cannot mediate viral entry into human cells, two mutations enabled it to do so by allowing it to be activated by human proteases. These mutations are present in MERS-CoV spike, explaining why MERS-CoV infects human cells. These mutations therefore played critical roles in the bat-to-human transmission of MERS-CoV, either directly or through intermediate hosts.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
Cell Line
Chiroptera / virology
Coronavirus Infections / genetics
Coronavirus Infections / transmission*
Coronavirus Infections / virology
Dipeptidyl Peptidase 4 / genetics*
Dipeptidyl Peptidase 4 / metabolism
Humans
Middle East Respiratory Syndrome Coronavirus / genetics
Middle East Respiratory Syndrome Coronavirus / metabolism*
Mutation
Receptors, Virus / genetics*
Viral Structural Proteins / genetics*

Substances

Receptors, Virus
Viral Structural Proteins
Dipeptidyl Peptidase 4

Abstract

Publication types

MeSH terms

Substances

Grants and funding