Researchers have identified a new strategy utilized by the varicella zoster virus (VZV), which leads to chickenpox and shingles, potentially enabling it to influence areas far from where it initially infects.
A team from the University of Colorado Anschutz Medical Campus has unveiled a novel evasion tactic of the varicella zoster virus, which results in chickenpox and shingles, possibly allowing it to impact tissues located distant from the initial infection site.
This finding was published in today’s Journal of Virology.
The researchers focused on a specific viral protein named IE62, packaged and transported throughout the body in tiny structures called small extracellular vesicles (sEVs). They found that IE62 contained in sEVs can move away from the infection site, entering cells and disabling their antiviral defenses, which paves the way for the virus’s spread.
The VZV is ancient and widely prevalent, present in 95% of the population. Its initial manifestation leads to chickenpox, which then becomes dormant. Later, during periods of stress, aging, or other influences, VZV may reactivate as shingles, a painful skin condition that can also affect the central nervous system and potentially lead to serious issues like vascular disease, stroke, dementia, and more.
For the virus to disseminate quickly throughout the body, it requires an effective method to evade immune responses. This study is the first to elucidate how this evasion occurs by leveraging the sEV machinery of infected cells.
“This is the first clear mechanism demonstrating how the virus can impact distant organs from the original infection site,” stated Christy Niemeyer, PhD, the primary author and assistant professor of neurology at the University of Colorado School of Medicine. “These vesicles effectively suppress the immune response.”
The senior author of the study, Andrew Bubak, PhD, also an assistant professor of neurology at CU School of Medicine, mentioned that the protein incapacitates the antiviral response in the cells much faster than previously recognized.
“We suspect this protein is being packaged into sEVs and transported via neurons to the skin, rendering skin cells susceptible to the entire infection,” Bubak explained. “We believe this occurs before the emergence of the rash, which is intriguing from a treatment perspective.”
Although there is a vaccine available for shingles, there are currently no therapies that target the action of this particular protein. However, that may change soon.
“This study is the first to pinpoint a new antiviral target that could lead to the development of new treatments,” Niemeyer noted.
Bubak remarked that this mechanism might account for the frequent co-infections and immunosuppressive effects observed in VZV patients. He also highlighted that the virus can reactivate intermittently in individuals without displaying the typical shingles rash, evading detection and prompting inquiries on whether such immunosuppressive events occur more often than previously believed.
“This mechanism could provide insights into how other viruses operate and cause infections,” he stated.
Niemeyer concurred, emphasizing that the role of sEVs in the virus’s spread necessitates further study.
“We need to better comprehend their role in viral dissemination and the development of secondary diseases to mitigate the systemic complications associated with VZV infections,” she concluded.
