Coronavirus Spike Protein and Tropism Changes

Adv Virus Res. 2016;96:29-57. doi: 10.1016/bs.aivir.2016.08.004. Epub 2016 Sep 13.

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.

Keywords: Coronavirus spike; Cross-species transmission; Cryo-EM structure; Membrane fusion; Receptor interaction; Tropism.

Publication types

  • Review

MeSH terms

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

Substances

  • Protein Subunits
  • Receptors, Virus
  • Spike Glycoprotein, Coronavirus