Evolution-Driven Attenuation of Alphaviruses Highlights Key Glycoprotein Determinants Regulating Viral Infectivity and Dissemination

Cell Rep. 2019 Jul 9;28(2):460-471.e5. doi: 10.1016/j.celrep.2019.06.022.


Understanding the fundamental mechanisms of arbovirus transmission and pathogenesis is essential to develop strategies for treatment and prevention. We previously took an in vivo evolution-based approach and identified the chikungunya virus E1 glycoprotein residue 80 to play a critical role in viral transmission and pathogenesis. In this study, we address the genetic conservation and function of position 80 and demonstrate that this residue is a key determinant in alphavirus infectivity and dissemination through modulation of viral fusion and cholesterol dependence. In addition, in studying the evolution of position 80, we identified a network of glycoprotein residues, including epidemic determinants, that regulate virus dissemination and infectivity. These studies underscore the importance of taking evolution-based approaches to not only identify key viral determinants driving arbovirus transmission and pathogenesis but also to uncover fundamental aspects of arbovirus biology.

Keywords: E1 glycoprotein; alphaviruses; chikungunya virus; cholesterol dependence; fusion; viral dissemination.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chikungunya virus / genetics*
  • Glycoproteins / metabolism*
  • Humans
  • Transfection
  • Viral Envelope Proteins / genetics*
  • Virus Diseases / genetics*
  • Virus Replication / genetics*


  • Glycoproteins
  • Viral Envelope Proteins