Antiviral responses are shaped by heterogeneity in viral replication dynamics

Lucas J M Bruurs, Micha Müller, Jelle G Schipper, Huib H Rabouw, Sanne Boersma, Frank J M van Kuppeveld, Marvin E Tanenbaum

Research output: Contribution to journal/periodicalArticleScientificpeer-review

3 Citations (Scopus)

Abstract

Antiviral signalling, which can be activated in host cells upon virus infection, restricts virus replication and communicates infection status to neighbouring cells. The antiviral response is heterogeneous, both quantitatively (efficiency of response activation) and qualitatively (transcribed antiviral gene set). To investigate the basis of this heterogeneity, we combined Virus Infection Real-time IMaging (VIRIM), a live-cell single-molecule imaging method, with real-time readouts of the dsRNA sensing pathway to analyse the response of human cells to encephalomyocarditis virus (EMCV) infection. We find that cell-to-cell heterogeneity in viral replication rates early in infection affect the efficiency of antiviral response activation, with lower replication rates leading to more antiviral response activation. Furthermore, we show that qualitatively distinct antiviral responses can be linked to the strength of the antiviral signalling pathway. Our analyses identify variation in early viral replication rates as an important parameter contributing to heterogeneity in antiviral response activation.

Original languageEnglish
Pages (from-to)2115-2129
Number of pages15
JournalNature Microbiology
Volume8
Issue number11
DOIs
Publication statusPublished - Nov 2023

Keywords

  • Humans
  • Virus Replication
  • Signal Transduction
  • Encephalomyocarditis virus/physiology
  • Antiviral Agents
  • Virus Diseases

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