title: Coronavirus Spike Protein and Tropism Changes.
abstract: Coronaviruses (CoVs) have a remarkable potential to change tropism. This is particularly illustrated over the last 15 years by the emergence of two zoonotic CoVs, the severe acute respiratory syndrome (SARS)- and Middle East respiratory syndrome (MERS)-CoV. Due to their inherent genetic variability, it is inevitable that new cross-species transmission events of these enveloped, positive-stranded RNA viruses will occur. Research into these medical and veterinary important pathogens-sparked by the SARS and MERS outbreaks-revealed important principles of inter- and intraspecies tropism changes. The primary determinant of CoV tropism is the viral spike (S) entry protein. Trimers of the S glycoproteins on the virion surface accommodate binding to a cell surface receptor and fusion of the viral and cellular membrane. Recently, high-resolution structures of two CoV S proteins have been elucidated by single-particle cryo-electron microscopy. Using this new structural insight, we review the changes in the S protein that relate to changes in virus tropism. Different concepts underlie these tropism changes at the cellular, tissue, and host species level, including the promiscuity or adaptability of S proteins to orthologous receptors, alterations in the proteolytic cleavage activation as well as changes in the S protein metastability. A thorough understanding of the key role of the S protein in CoV entry is critical to further our understanding of virus cross-species transmission and pathogenesis and for development of intervention strategies.
authors.affiliation: Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: R J G
authors.initials: RJ
authors.lastname: Hulswit
authors.affiliation: Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. Electronic address: c.a.m.dehaan@uu.nl.
authors.forename: C A M
authors.initials: CA
authors.lastname: de Haan
authors.affiliation: Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands. Electronic address: b.j.bosch@uu.nl.
authors.forename: B-J
authors.initials: BJ
authors.lastname: Bosch
mesh_terms: D000818:Animals; D015870:Gene Expression; D014644:Genetic Variation; D006801:Humans; D065207:Middle East Respiratory Syndrome Coronavirus / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D008958:Models, Molecular; D011487:Protein Conformation; D000072417:Protein Domains; D021122:Protein Subunits / Q000737:chemistry* / Q000235:genetics; D059748:Proteolysis; D011991:Receptors, Virus / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure; D045473:Severe acute respiratory syndrome-related coronavirus / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D064370:Spike Glycoprotein, Coronavirus / Q000737:chemistry* / Q000235:genetics / Q000648:ultrastructure; D056189:Viral Tropism; D014771:Virion / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D053586:Virus Internalization
chemical_list: D021122:Protein Subunits; D011991:Receptors, Virus; D064370:Spike Glycoprotein, Coronavirus
keywords: Coronavirus spike; Cross-species transmission; Cryo-EM structure; Membrane fusion; Receptor interaction; Tropism