Nanoscale polarization of the entry fusion complex of vaccinia virus drives efficient fusion

Robert D.M. Gray, David Albrecht, Corina Beerli, Moona Huttunen, Gary H. Cohen, Ian J. White, Jemima J. Burden, Ricardo Henriques*, Jason Mercer

*Corresponding author for this work

Research output: Contribution to journalLetterpeer-review

8 Citations (Scopus)

Abstract

To achieve efficient binding and subsequent fusion, most enveloped viruses encode between one and five proteins1. For many viruses, the clustering of fusion proteins—and their distribution on virus particles—is crucial for fusion activity2,3. Poxviruses, the most complex mammalian viruses, dedicate 15 proteins to binding and membrane fusion4. However, the spatial organization of these proteins and how this influences fusion activity is unknown. Here, we show that the membrane of vaccinia virus is organized into distinct functional domains that are critical for the efficiency of membrane fusion. Using super-resolution microscopy and single-particle analysis, we found that the fusion machinery of vaccinia virus resides exclusively in clusters at virion tips. Repression of individual components of the fusion complex disrupts fusion-machinery polarization, consistent with the reported loss of fusion activity5. Furthermore, we show that displacement of functional fusion complexes from virion tips disrupts the formation of fusion pores and infection kinetics. Our results demonstrate how the protein architecture of poxviruses directly contributes to the efficiency of membrane fusion, and suggest that nanoscale organization may be an intrinsic property of these viruses to assure successful infection.

Original languageEnglish
Pages (from-to)1636-1644
Number of pages9
JournalNature Microbiology
Volume4
Issue number10
Early online date8 Jul 2019
DOIs
Publication statusPublished - Oct 2019

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Applied Microbiology and Biotechnology
  • Genetics
  • Microbiology (medical)
  • Cell Biology

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