Defective viral genomes alter how Sendai virus interacts with cellular trafficking machinery, leading to heterogeneity in the production of viral particles among infected cells

Emmanuelle Genoyer, Carolina B. López

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

Defective viral genomes (DVGs) generated during RNA virus replication determine infection outcome by triggering innate immunity, diminishing virulence, and, in many cases, facilitating the establishment of persistent infections. Despite their critical role during virus-host interactions, the mechanisms regulating the production and propagation of DVGs are poorly understood. Visualization of viral genomes using RNA fluorescent in situ hybridization revealed a striking difference in the intracellular localization of DVGs and full-length viral genomes during infections with the paramyxovirus Sendai virus. In cells enriched in full-length virus, viral genomes clustered in a perinuclear region and associated with cellular trafficking machinery, including microtubules and the GTPase Rab11a. However, in cells enriched in DVGs, defective genomes distributed diffusely throughout the cytoplasm and failed to interact with this cellular machinery. Consequently, cells enriched in full-length genomes produced both DVG- and full-length-genome-containing viral particles, while DVG-high cells poorly produced viral particles yet strongly stimulated antiviral immunity. These findings reveal the selective production of both standard and DVG-containing particles by a subpopulation of infected cells that can be differentiated by the intracellular localization of DVGs. This study highlights the importance of considering this functional heterogeneity in analyses of virus-host interactions during infection.

Original languageEnglish
Article numbere0157918
JournalJournal of virology
Volume93
Issue number4
DOIs
StatePublished - Feb 1 2019

Keywords

  • Defective interfering particles
  • Defective viral genomes
  • Infection heterogeneity
  • Paramyxovirus
  • Particle production

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