Have Researchers Uncovered the Viral Achilles Heel?

Viruses have an exceptional ability to circumvent the body's immune system and cause diseases. The majority of people recover from a viral infection such as influenza, although the current COVID-19 pandemic demonstrates how dangerous viruses are when there is no effective vaccine or treatment.

Professor and virologist Søren Riis Paludan from the Department of Biomedicine at Aarhus University, Denmark, has been leading a research partnership between Aarhus University, the University of Oxford and the University of Gothenburg, which has brought us one step closer to understanding the tactics used by viruses when they attack the immune system.

Søren Riis Paludan heads a laboratory which carries out research into the immune system's ability to fight diseases caused by the herpes virus, influenza viruses and, most recently, SARS-CoV2, more commonly known as coronavirus.

In the new study, which has just been published in the scientific journal Journal of Experimental Medicine, the researchers have investigated how the herpes simplex virus circumvents the immune system in order to cause infections of the brain. This is a rare infection but one which has a high mortality rate among those who are affected.

"In the study, we found that the herpes simplex virus is capable of inhibiting a protein in the cells, known as STING, which is activated when there is a threat. When STING is inhibited, the body's immune system is also inhibited - the virus thereby puts the brakes on the body's brake, which is supposed to prevent us from becoming ill. Other viruses also make use of the same principle," says Søren Riis Paludan.

Søren Riis Paludan points out that though the study focuses on herpesviruses, there are parallels to the coronavirus. Interestingly, the same protein is also inhibited by many different viruses, including the coronavirus.

"This suggests that we have found an Achilles heel in the virus and the way it establishes infections in the body. Our results lead us to hope that if we can prevent viruses from blocking STING, then we can prevent the virus from replicating. That could pave the way for new principles for treatment of herpes, influenza and also the coronavirus," says Søren Riis Paludan.

He hopes that the research results can be used in the development of antiviral drugs and vaccines in the future.

"Previous studies have also shown that the coronavirus inhibits STING in the same way as the herpes virus. This suggests that we have found a common denominator for several types of virus, and that this is probably an important element in the development of treatment," he says.

Reference
HSV1 VP1-2 deubiquitinates STING to block type I interferon expression and promote brain infection. Chiranjeevi Bodda et al. J Exp Med (2020) 217 (7): e20191422. https://doi.org/10.1084/jem.20191422.

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