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.
PY - 2023
Y1 - 2023
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.
UR - http://www.scopus.com/inward/record.url?scp=85173960686&partnerID=8YFLogxK
U2 - 10.1038/s41564-023-01501-z
DO - 10.1038/s41564-023-01501-z
M3 - Article
C2 - 37814072
AN - SCOPUS:85173960686
SN - 2058-5276
VL - 8
SP - 2115
EP - 2129
JO - Nature Microbiology
JF - Nature Microbiology
IS - 11
ER -