During the 2009 H1N1 influenza pandemic, there was a marked increase in neurological complications such as febrile seizures, encephalopathy or encephalitis, delirium, and focal neurologic syndromes, as reported in several studies. Neurological complications have been associated with many other viruses as well ; including but not limited to Zika Virus; SARS-CoV-2, which causes COVID-19; and Varicella-Zoster Virus, which causes chickenpox.
Scientists have now learned more about a genetic variant that links viral infections to neurodegenerative diseases. In this study, the researchers found a specific variation in a gene that alters mitochondria, causing a disruption in the cellular antiviral response. This work, which has been reported in Nature, has identified mitochondria as an important part of viral connection to neurodegeneration.
While mitochondria are popularly known as the powerhouse of the cell, they have a variety of roles, and help protect cels from stress. Mitochondria are also related to immune system function. Dysfunction in mitochondria has been associated with some diseases that affect the brain, and liver disorders.
An enzyme that is important to mitochondria called POLG can be affected by a genetic variant. This work showed that the POLG variant weakens and delays the initial immune response to a viral infection, which is then followed by a overactivated but late reaction that disrupts that brain and liver.
This variation in the POLG gene goes back to the times of Vikings, and can now be found throughout the European population. Northern Europeans are particularly high carriers of this variant, and about one in one hundred people in Finland and Norway are carriers.
If someone inherits two copies of the POLG variant, a disease called MIRAS (mitochondrial recessive ataxia syndrome) arises. The presentation of MIRAS can differ greatly from one patient to another, so researchers have wondered whether other influences affect the manifestation of the disease. This work may explain why some MIRAS patients have severe epilepsy as teenagers while others only have symptoms years or even decades later - viral infections may be a trigger.
"Our results indicate that external factors, such as viral infections, can modify manifestation and age-of-onset of neurological diseases," explained study co-author and postdoctoral scientist Yilin Kang, PhD of the University of Helsinki. "Identification of susceptibility factors and triggering mechanisms are valuable targets for new therapy developments. The current findings indicate the importance of new mitochondrial functions in maintaining brain health."
Sources: University of Helsinki, Nature