9 October 2023 New insights into factors that affect cell’s antiviral response against infection Back to news The rate at which a virus replicates in a cell affects the cell’s ability to fight off the infection. Viral infections that proceed slower are more likely to trigger an antiviral response. That is what researchers from the groups of Marvin Tanenbaum (Hubrecht Institute) and Frank van Kuppeveld (Universiteit Utrecht) discovered. They used new microscopy techniques to visualize the competition between virus and cell in the first hours after infection and published their results in Nature Microbiology on 9 October 2023. Every cell contains a basic yet effective antiviral response mechanism that can be activated when a virus invades. With this mechanism, the cell tries to prevent the intruder from taking over the cell and replicating itself. Additionally, the cell’s antiviral response signals to nearby cells so they can arm themselves against the virus. However, the virus tries to sabotage this defense mechanism, leading to a battle between the cell and the virus. The outcome of this competition is likely to have major consequences for the cell’s ability to clear the virus. Viral infection leads to activation of antiviral response in a fraction of all infected cells. Cells infected with virus (in white) can sometimes trigger an antiviral response. This activates genes that are involved in the defense against the virus (green and pink dots). Credit: Lucas Bruurs, copyright: Hubrecht Instituut. Replication rate Researchers from the Hubrecht Institute and Utrecht University previously developed an advanced technique that allows them to live visualize the progress of a virus infection in living cells. Now they have combined this technique called VIRIM (Virus Infection Real-time Imaging) with new technology to specifically visualize the antiviral response and gain more insight into the factors that influence the outcome of the competition between cell and virus. Lucas Bruurs, the lead researcher in the project, says: “We saw that the rate at which a virus multiplies in the first hours after an infection influences the cell’s ability to resist. The cell’s antiviral response is activated more often in infections that proceed more slowly.” Sabotage by virus The results were not entirely expected. “When a virus replicates, a certain type of RNA is produced. The cell recognizes this RNA molecule as foreign, and therefore knows that there is an intruder and activates the antiviral response. But with a slower infection, it takes longer before the viral RNA is produced. You would expect that it also takes longer before the cell activates its defense mechanism,” Bruurs explains. But the cell seems to effectively activate the antiviral response in these cases, probably because the virus is less capable of sabotaging it. Better treatments against viral infections The results provide insight into the factors that determine the outcome of the competition between virus and cell. Bruurs: “If we better understand this process, we can develop new treatments to effectively combat viral infections in the future.” But before that is possible, the researchers must investigate other factors that play a role in the progression of an infection. “The techniques we have now developed can help with that,” Bruurs concludes. Real-time imaging of viral replication and antiviral response in individual cells. Left: virus replication is visualized using VIRIM. The first stages of virus replication (green dots). Middle and right: the translocation of the molecule IRF3 (middle) and transcriptional activation of target gene IFIT1 (right) show that the antiviral response is activated. Credit: Lucas Bruurs, copyright Hubrecht Institute Publicatie 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 and Marvin E. Tanenbaum. Nature Microbiology 2023. Marvin Tanenbaum is group leader at the Hubrecht Institute, professor of Gene Expression Dynamics at TU Delft and Oncode Investigator.
