New strategy to protect from severe COVID-19
SARS-CoV-2 viruses can hide from recognition by the immune system when infecting cells, thereby delaying the onset of the immune response. Scientists around Prof Gunther Hartmann from the University Hospital Bonn and the German Center for Infection Research (DZIF) now demonstrated in a mouse model that stimulation of a special cellular virus-detecting immune receptor can lead to early activation of the immune response and hence an overall faster reaction to viral infection. Stimulation of the immune system not only improved protection from fatal SARS-CoV-2 infection but also significantly reduced the frequency and progression of severe disease.
The ongoing SARS-CoV-2 pandemic and emergence of new SARS-CoV-2 variants has revealed an urgent need for antiviral therapeutic drugs and vaccines.
Normally, the immune system is able to identify invading viral genetic materials and triggers a response. However, SARS-CoV-2 proteins can modify viral ribonucleic acid (RNA) molecules such that they become indistinguishable from the host’s own RNA molecules.
Disguise protects the virus from the immune system
SARS-CoV-2 carries a molecular tool box that allows the virus to evade recognition by the immune system. Among its tools are several proteins that inhibit antiviral recognition systems of infected cells. For instance, viral RNA molecules can be masked by the addition of methyl groups. As a result, the viral RNA escapes early recognition by the central immune-receptor RIG-I (retinoic acid-inducible gene I). This receptor normally induces an important type of immune response in which antiviral active proteins, cell signals and messenger substances − such as type I interferon (IFN) − are generated.
"A robust, early type I IFN production is key to clearing SARS-CoV-2 infection. Its absence is associated with disease progression and the development of severe COVID-19," explains study co-author Prof Eva Bartok. This type of immune response typically occurs only a few days after infection and – besides viral RNA-triggered activation of RIG-I − involves the activation of further immune cells and ultimately the production of antibodies.
In the present study, the scientists analysed the effect of synthetic RNA on the immune response and the progression of SARS-CoV-2 infection and COVID-19 disease in a mouse model.
Mouse model mimics human COVID-19 disease
As mice are generally not susceptible to SARS-CoV-2, the researchers used genetically adapted mice that express the cellular SARS-CoV-2 binding protein ACE2.
Using this model, the researchers could show that a systemic application of synthetic RNA one to seven days prior to infection or one day after infection with SARS-CoV-2 drastically reduced the rate of fatal infections.
“Our findings show that targeting RIG-I either prophylactically or therapeutically could be a promising approach in the treatment of COVID-19. Prior to application in humans, however, further studies are needed,” summarises study lead Prof Gunther Hartmann the research findings.
Participating institutions and funding:
In addition to the Institute of Clinical Chemistry and Clinical Pharmacology, the Institute of Virology, the Institute of Cardiovascular Immunology and the Mildred Scheel School of Oncology at the University Hospital Bonn, the German Center for Infection Research and the Institute of Tropical Medicine, Antwerp, Belgium were involved. The study was mainly funded by the German Research Foundation (DFG).
Source: Press release of the University of Bonn
