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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.

Original publication

DOI

10.1016/bs.aivir.2016.08.004

Type

Chapter

Publication Date

01/2016

Volume

96

Pages

29 - 57

Addresses

Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.

Keywords

Animals, Humans, SARS Virus, Virion, Receptors, Virus, Protein Subunits, Gene Expression, Protein Conformation, Models, Molecular, Virus Internalization, Genetic Variation, Viral Tropism, Proteolysis, Spike Glycoprotein, Coronavirus, Middle East Respiratory Syndrome Coronavirus, Protein Domains