Recent research from Stony Brook University has shed new light on the severe neurological impacts of the Powassan virus (POWV).
The study was led by virologist Erich Mackow, Ph.D., at Stony Brook’s Renaissance School of Medicine (RSOM). This study could significantly advance the understanding of this dangerous virus and contribute to the development of targeted vaccines and therapeutics.
POWV, primarily found in North America, can be transmitted through a tick bite in as little as 15 minutes. The virus is present in 2% of ticks on Long Island and infected individuals are at a 10% risk of fatal encephalitis — the inflammation of brain tissue.
Mackow is at the forefront of the research aimed at revealing the complexities of POWV-induced encephalitis. His team is dedicated to exploring various aspects of POWV infection, including the role of age in disease severity and the development of therapeutics and vaccines.
In the Journal of Virology, the research team has made significant efforts by isolating a POWV strain (L19) from deer ticks on Long Island and establishing a murine model that replicates the age-dependent lethality observed in humans.
“We found that POWV enters the brain and causes visible neurological damage to all mice, regardless of age,” Megan Mladinich, Ph.D., a member of Mackow’s research team, said. “However, aged mice alone have higher levels of virus present in their brains.”
From this, the team determined that POWV lethality increases more than tenfold with age and identified that the increased lethality is associated with the activation of central nervous system glial cells and age-dependent neuroinflammatory responses.
The study also highlights the differential activation of microglial phenotypes in response to POWV infection where M1 (neuroprotective) and M2 (neurodegenerative) phenotypes were assessed in young versus aged mice.
In young mice, neuroprotective cytokines (small signaling proteins that help control inflammation) are predominantly present, while aged mice exhibit a predominance of neurodegenerative cytokines. Understanding these differences is crucial for developing therapeutics that can modulate the M2 phenotype in older populations to mitigate neurodegenerative outcomes.
Mackow provided additional context about the clinical relevance of the findings. Symptoms of POWV infection typically develop one to five weeks after a tick bite, starting with febrile illness.
“While human cases are rare and often asymptomatic, severe disease is more common in individuals over 60 years old,” Mackow said.
Young children may also experience severe neurological symptoms but often recover completely, suggesting age-related differences in disease outcomes and recovery processes.
Mackow also mentions ongoing work developing an attenuated POWV strain for vaccine use. By using recombinant virus technology, the team aims to create a stable, attenuated vaccine that does not revert to its original form. This approach, involving multiple mutations to ensure virus attenuation, is critical for creating a safe and effective vaccine.
“The more we can understand about POWV infection starting from the bite site to POWV entry and replication in the brain, the better we can target it,” Mladinich said.
Mackow’s research is supported by $9 million in funding from the United States Department of Defense and three National Institutes of Health grants from the National Institute of Allergy and Infectious Diseases.
