Suffolk Reporter

Stony Brook, NY, August 20, 2024 – While Lyme disease is the most recognized tick-borne disease in the United States, other infections transmitted through tick bites can be equally or more dangerous. One of these is the Powassan virus (POWV). Erich Mackow, PhD, a virologist at Stony Brook University, is researching one of the most dangerous effects of POWV – neurologic damage.

Powassan virus is endemic to North America and present in about two percent of Long Island ticks. It can be injected into the skin during just a 15-minute tick bite. Patients infected with POWV have a 10 percent risk of fatal encephalitis and up to 50 percent experience long-term neurologic damage. Severe neurologic symptoms are particularly associated with older patients.

Mackow is a Professor in the Department of Microbiology and Immunology in the Renaissance School of Medicine (RSOM) and a core member of Stony Brook’s Center for Infectious Diseases. He is among several scientists at Stony Brook University investigating better treatments for tick-borne infections. Stony Brook Medicine has a clinic dedicated to treating Lyme disease and all tick-borne infections, including POWV, and hosts the Regional Tick-Borne Disease Resource Center.

“The severity of Powassan encephalitis in the elderly remains an enigma as the mechanisms of the viral neuroinvasion remain virtually unknown,” says Mackow.

For this research, Mackow and his RSOM colleagues focus on analyzing all aspects of POWV's neurological effects. They define viral proteins that direct neurovirulence, develop therapeutics and attenuated POWV vaccines, and assess cell senescence's role as an age-dependent cause of POWV encephalitis.

The team isolated a Powassan virus strain (L19) from ticks on Long Island and developed an animal model for POWV-induced encephalitis and age-dependent lethality. They established a mechanism for genetically altering POWV and generated attenuated viral mutants that serve as vaccine candidates which fail to cause disease but elicit protective immune responses.

Vaccines and therapeutic approaches for preventing POWV neuroinvasion are now being examined by researchers who have revealed the role of age in infection severity.

“Our findings provide a foundational basis to understanding the mechanism of neurovirulent pathogens in the central nervous system," explains Mackow. "They define brain senescence's role in disease severity and offer potential targeted human therapeutics that protect the elderly from lethal POWV infections."

The investigators detail their discovery based on an age-dependent model and novel POWV genetics in a new paper published this month in the Journal of Virology.

The authors write that their laboratory results establish age-dependent lethality of POWV in a murine model mirroring human severity and long-term central nervous system pathology in older individuals.

Mackow noted that only minimal infectious doses were highly lethal in older mice with lethality increasing more than tenfold with age. The researchers also determined that POWV lethality is linked to central nervous system glial cell activation and age-dependent neuroinflammatory cytokine responses in mice, establishing mechanisms contributing to Powassan virus encephalitis.

Mackow’s research is supported by grants totaling approximately $9 million through August 2029 from both the Department of Defense (DOD) and National Institutes of Health (NIH). These funds aim to better understand mechanisms by which POWV enters its host's brain, identify age-dependent responses increasing disease severity, and develop therapeutics and vaccines against it.