Published on 17 December 2025

Blog Reto Lang – the role of stress granules in viral infections

“Our work provides an in-depth insight into the way viruses interact with the cellular stress response, and into the role of stress granules in infections”

Viral infections as stressors: unlocking cellular stress response during viral infections

The cells of living organisms experience various stressors, such as nutrient deficiencies, contact with toxins, and viral infections. In order to prevent damage to the cell and to adapt to stress, cells have developed a stress response. One characteristic of this response is the formation of what are known as stress granules (SGs), which are assemblies of different proteins and mRNA in the cell. The function of these stress granules is still not completely understood. Scientists assume, however, that they regulate a wide range of cellular processes, such as the production of proteins and the suppression of programmed cell death, thereby helping the cell cope with stress.

In connection with infections it was found that some viruses manipulate or completely suppress the formation of stress granules in the cell. This resulted in stress granules also being attributed a role in immune response, although this is still disputed.

Interview with Dr Reto Lang

• What was the aim of your doctoral thesis?

  My thesis aimed to take a closer look at the cellular stress response during viral infections. We were particularly interested in stress granules and their protein composition. We wanted to understand whether viral infections lead to the formation of a specialised type of stress granule that is distinct from normal stress granules and is more closely connected to antiviral immune response.
  
  To do so, we compared stress granule formation during infection with two different viruses that are often used in the lab as model viruses: mouse hepatitis virus (MHV), which is a coronavirus, and Semliki Forest virus (SFV), which is a member of the alphavirus family.

• What are the main findings of your thesis?

  On the one hand, we observed that the viruses used didn’t induce any specialised stress granules, contradicting the hypothesis of an antiviral stress granule type. Interestingly, we discovered that there are significant differences in the granules between SFV and MHV, both in terms of when they appear during the infection and their protein composition.
  
  While the SFV stress granules are very similar to normal stress granules and are eliminated as the infection progresses, the MHV ones have a smaller proportion of certain proteins and are formed later. From this we conclude that the two viruses handle the cellular stress response very differently, and the stress granules play a different role depending on the virus.

• To what extent will your findings help to advance research?

  Our work provides a deeper insight into the interaction between viruses and cellular stress response, allowing us to draw conclusions about the role of stress granules during various viral infections. In particular, our observation that different viruses lead to the formation of very different stress granules, and that the characteristics of these granules appear to be heavily influenced by the virus in question, is an important finding. Researching stress granule formation during different viral infections helps us better understand the interplay between the virus and the host cell, which can serve as a basis for developing new antiviral drugs.

• What aspect of this work are you particularly proud of?

  The stress granule project in Prof. Volker Thiel’s research group had already been launched several years before I joined the IVI and is a collaborative project over several ‘generations’ of students. I’m proud to have been a part of this project and I’m really pleased that we have been able to wrap it up with a publication.

• What did you especially like about working on your thesis?

  I’ve always been fascinated by microscopy images, whether of microorganisms or individual cells. What I found really fascinating was being able to use different microscopy techniques to visualise the microscopic world of cells, which in ordinary circumstances remains invisible to us. Besides the scientific aspect, I really liked the working environment and the many great people I dealt with.

  

  Figure 1: Mouse cells infected with MHV. The red colour represents the virus (viral, double-stranded RNA), the green colour shows the stress granules and the blue is the cell nucleus. The cells were coloured eight hours after the infection and subsequently examined under a fluorescence microscope.

• How was your time at the IVI?

  My time at the IVI has been amazing and very instructive. As well as the fascinating research topics, I’ve also really appreciated the great atmosphere in our research group, and in the institute as a whole. I’d like to sincerely thank all those who have helped and supported me during my time at the IVI, and who have made stressful times much more bearable. I’m pleased to be able to stay on and enjoy a few more months here.

• What’s next for you?

  Until the spring of next year I’m staying in Prof. Volker Thiel’s research group to tie up a few projects. After that I’ll be focussing on my private life, at least for a few months, marrying my long-term girlfriend, and going on an extended trip to northern Europe. I’m still thinking about whether to stay in academia after that or whether to go into industry.

Glossary

• Stress granules

  Stress granules are tiny aggregates composed of proteins and RNA molecules that form in cells in response to stress, such as infection, temperature shock or food withdrawal. They help to protect the cell by stopping production of unnecessary proteins and focusing on damage repair. Stress granules can also be exploited by viruses to promote their own replication in the cell. Some viruses are able to inhibit or manipulate stress granulation in order to bypass the antiviral immune response and replicate themselves.

• Murine hepatitis virus (MHV)

  Murine hepatitis virus (MHV) is a coronavirus that infects mice, causing liver disease. It is related to SARS-CoV-2, SARS-CoV and MERS-CoV and is often used in science as a model virus for the study of coronaviruses.

Link to the publication

• Stress granules formed during different RNA virus infections show remarkable plasticity and substantial virus-specific differences in their formation and composition

Authors

Reto M. Lang, Silvio Steiner, Jenna Kelly, Anne-Christine Uldry, Pratik Dave, Sophie Braga-Lagache, Jeffrey Chao, Manfred Heller, Volker Thiel

Informations

• Blog Silvio Steiner Virus-host dynamics: how coronaviruses undermine cellular defence systems
• Coronaviruses cause respiratory and enteric viral infections and zoonoses