For many people, getting chickenpox is a rite of passage in childhood. About 95 percent of people carry the virus that causes the illness, known as varicella zoster virus (VZV). While the itchy rash of chickenpox is usually mild, VZV can linger in the body dormant for decades, only to emerge much later in life to cause shingles. Shingles is a far more serious condition that also affects the skin. But it can impact the nervous system as well. It is known for being painful, and can lead to complications like stroke, dementia, and vascular disease.
Scientists have now learned more about how VZV can evade the immune system to infect tissues that are nowhere near the original infection site. The findings have been reported in the Journal of Virology.
This study used animal models and human cells growing in culture to reveal that VZV produces a protein called IE62. This protein is contained within cellular packages known as small extracellular vesicles (sEVs) and then shuttled around the body. The virus moves into sEVs by exploiting the host cell's machinery. Once inside of sEVs, IE62 can move away from the infection site to invade other cells. The protein can disrupt the immune system's antiviral strategies to cause additional infection.
“This is the first time a clear mechanism has been found that actually ties this virus to an avenue by which it can affect distal organs, far from the site of infection,” said first study author Christy Niemeyer, PhD, an assistant professor of neurology at the University of Colorado School of Medicine. “These vesicles shut down the immune response.”
This immune evasion strategy is also triggered far earlier than we knew, noted senior study author Andrew Bubak, PhD, assistant professor of neurology at the CU School of Medicine.
“We believe this protein is likely being packaged into sEVs and shuttled down the neurons that go to your skin, making the cells under the skin vulnerable to the whole infection,” Bubak said. “We think this precedes the rash, which is obviously interesting from a therapeutic standpoint.”
Although there is a shingles vaccine, there are no treatments that target IE62. The study authors noted that this work may change that, however.
This mechanism may also apply to other viruses as well, they noted.
“We need to better understand their role in viral spread and secondary disease development to reduce the systemic complications caused by VZV infections,” said Niemeyer.
Sources: University of Colorado Anschutz Medical Campus, Journal of Virology