Antiviral responses are shaped by heterogeneity in viral replication dynamics

TY - JOUR

T1 - Antiviral responses are shaped by heterogeneity in viral replication dynamics

AU - Bruurs, Lucas J M

AU - Müller, Micha

AU - Schipper, Jelle G

AU - Rabouw, Huib H

AU - Boersma, Sanne

AU - van Kuppeveld, Frank J M

AU - Tanenbaum, Marvin E

N1 - © 2023. The Author(s).

PY - 2023/11

Y1 - 2023/11

N2 - 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.

AB - 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.

KW - Humans

KW - Virus Replication

KW - Signal Transduction

KW - Encephalomyocarditis virus/physiology

KW - Antiviral Agents

KW - Virus Diseases

U2 - 10.1038/s41564-023-01501-z

DO - 10.1038/s41564-023-01501-z

M3 - Article

C2 - 37814072

SN - 2058-5276

VL - 8

SP - 2115

EP - 2129

JO - Nature Microbiology

JF - Nature Microbiology

IS - 11

ER -