title: Two Mutations Were Critical for Bat-to-Human Transmission of Middle East Respiratory Syndrome Coronavirus.
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.
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York, USA.
authors.forename: Lanying
authors.initials: L
authors.lastname: Du
authors.affiliation: 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.
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
authors.forename: Zhengli
authors.initials: Z
authors.lastname: Shi
authors.affiliation: Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA.
authors.forename: Ralph S
authors.initials: RS
authors.lastname: Baric
authors.affiliation: Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota, USA lifang@umn.edu.
authors.forename: Fang
authors.initials: F
authors.lastname: Li
mesh_terms: D000818:Animals; D002460:Cell Line; D002685:Chiroptera / Q000821:virology; D018352:Coronavirus Infections / Q000235:genetics / Q000635:transmission* / Q000821:virology; D018819:Dipeptidyl Peptidase 4 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D065207:Middle East Respiratory Syndrome Coronavirus / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011991:Receptors, Virus / Q000235:genetics*; D015678:Viral Structural Proteins / Q000235:genetics*
chemical_list: D011991:Receptors, Virus; D015678:Viral Structural Proteins; D018819:Dipeptidyl Peptidase 4