How a dormant viral infection can reactivate and trigger a stroke

Scientists at the University of Colorado Anschutz Medical Campus believe they have discovered how a common disease called shingles can increase a person’s risk of stroke. The novel findings reveal how latent viral infections can be reawakened after lying dormant for years and cause health issues beyond a mild acute disease.

Most people are infected with varicella-zoster virus (VZV) in childhood, and for some it can lead to a disease known as chickenpox. Despite most signs of the illness quickly resolving in many people the virus itself doesn’t every really go away. Instead, it often remains dormant in our central nervous system.

In around 30% of people, at some point in their life, the VZV virus reawakens and again causes disease. This time round the illness is called shingles. For most people shingles is characterized by a rash but a number of other health complications can accompany a case of the disease.

“Most people know about the painful rash associated with shingles, but they may not know that the risk of stroke is elevated for a year after infection,” explained Andrew Bubak, lead author on the new study. “Importantly, the rash is often completely healed and individuals feel normal but nonetheless are walking around with this significant elevation in stroke risk.”

The question Bubak and colleagues set out to answer was exactly how a reactivated varicella-zoster virus could be increasing a person’s risk of stroke. The researchers suspected it had something to do with tiny, sac-like molecules called exosomes. These molecules are formed within cells and carry cargo to tissue in other parts of the body.

The hypothesis was that the reactivated virus triggered the production of exosomes carrying blood clotting proteins. So, to investigate, the researchers isolated exosomes from 10 healthy subjects and 13 patients with shingles.

The findings revealed exosomes from shingles patients contained significantly higher volumes of clotting proteins than exosomes from healthy subjects. And even more strikingly, those levels were still elevated when samples were taken from the shingles patients three months after their acute illness had subsided.

“To functionally confirm that the contents of these exosomes can induce clotting, we exposed platelets – cell fragments involved in blood clotting – of healthy people to exosomes from either shingles patients or healthy people,” Bubak explained in an article for The Conversation. “We found that exposing platelets to shingles exosomes triggered them to clump together and form aggregates with other types of blood cells, as they would in forming a blood clot.”

An increased risk of stroke has been linked to the aftermath of other viral infections, including influenza and COVID-19. However, at this point the research only focuses on stroke risk in relation to VZV infection, so it’s unclear whether this mechanism plays a role in the relationship between stroke and other viral illnesses.

According to Bubak there is plenty more work to be done to better understand the relationship between stroke and viral infections, but in the short-term these novel findings could help inform clinical practice. A vaccine to prevent shingles has been approved for adults over the age of 50 but there are also anti-platelet drugs that could be given to shingles patients most at risk of stroke.

“If these findings are confirmed with a larger longitudinal study, then this could change clinical practice,” said Bubak. “… it’s really important and so easily mitigated. Send them home with antiplatelet agents.”

The new study was published in The Journal of Infectious Diseases.

Source: University of Colorado Anschutz Medical Campus

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