Boosting the immune system’s infection-preventing ability
The complex network of cells, organs and proteins that make up the human immune system is our first line of defence against disease. While it does a rather incredible job of patrolling the body and eliminating harmful invaders such as viruses and bacteria, sometimes it benefits from a bit of a boost – which is exactly what it gets whenever we receive a vaccine, medicine or therapy. But what if we could do more to help the immune system better respond against infection? “Understanding how the immune system interacts with specific viruses and how this interaction impacts the pathogenesis of viral infections could be the key to developing improved vaccines, updated antiviral therapeutics and advanced diagnostic tools,” says Søren Riis Paludan, a professor of Biomedicine at Aarhus University. With the support of the EU-funded ENVISION project, Paludan aims to cut such a key. “Our goal is to identify novel mechanisms through which cells fight infections while also providing information on the cellular signalling pathways that promote defence and disease during infection,” he adds.
Opening the door to new therapies for treating herpes simplex encephalitis
The most important result coming from the project’s research is the discovery of TMEFF1 as the first neuron-specific antiviral restriction factor for herpes simplex encephalitis (HSE) in humans. HSE is a rare yet serious infection that occurs when the herpes simplex virus (HSV) travels to the brain and infects its cells. “On the one hand we demonstrated that the presence of TMEFF1 can help prevent HSV brain infection by restricting the virus’ ability to enter the brain’s cortical neurons while, on the other, we showed how an inherited TMEFF1 deficiency renders a person more susceptible to infection,” explains Paludan. According to Paludan, TMEFF1’s preventative role could be leveraged to develop new ways of treating HSE.
Eliminating viruses before they cause infection
The European Research Council supported project also studied the hypoxia-inducible factor (HIF) pathway, a cellular signalling system that regulates cellular responses to low oxygen levels, and autophagy, a cellular process that involves the self-digestion of damaged or unnecessary cellular components. “Here we uncovered the crucial early host defence role that HIF and autophagy play, eliminating or reducing a wide range of different viruses before they can cause serious infection,” notes Paludan. Researchers further used molecular studies and mouse models to identify how the DNA-activated cGAS-STING immune pathway is activated during infection by DNA viruses. “We discovered that this pathway is essential to activating host defence in the brain, mainly in the cell type called microglia,” adds Paludan.
Identifying novel antiviral mechanisms
In addition to its many scientific achievements, the project also trained the next generation of biomedicine scientists. These scientists, together with Paludan, will now look to identify novel antiviral mechanisms, with a particular focus on the brain. They will also work to characterise the physiological roles of these mechanisms in viral diseases. “ENVISION may be over, but we will continue working on some of the project’s most important findings as there is still a lot to learn about these new molecules and pathways,” concludes Paludan.
Keywords
ENVISION, immune system, infection, antiviral, vaccines, disease, medicine, herpes simplex encephalitis, herpes simplex virus, biomedicine
