While Lyme disease is the most recognized and prevalent tick-borne disease in the United States, other infections transmitted through tick bites can be equally or even more dangerous, including the Powassan virus (POWV). Erich Mackow, an internationally recognized virologist at Stony Brook University, is conducting research to uncover one of the most dangerous effects of POWV — neurologic damage.
Powassan virus is endemic to North America. It is present in about 2 percent of Long Island ticks and is injected into the skin during just a 15-minute tick bite. POWV-infected patients have a 10 percent risk of fatal encephalitis and up to 50 percent of infected patients have long-term neurologic damage. Severe neurologic symptoms are associated with POWV infection in older patients.
Mackow is a professor in the Department of Microbiology and Immunology in the Renaissance School of Medicine (RSOM), a core member of Stony Brook’s Center for Infectious Diseases, and among several scientists at Stony Brook University investigating ways to better target treatments for tick-borne infections. Stony Brook Medicine has a clinic dedicated to treating Lyme disease and all tick-borne infections, such as POWV, and is home to the Regional Tick-Borne Disease Resource Center.
“The severity of Powassan encephalitis in the elderly remains an enigma as the mechanisms of viral neuroinvasion remain virtually unknown,” Mackow said.
For this research, Mackow and his RSOM colleagues focus their investigation on analyzing all aspects of the neurological effects of POWV, defining viral proteins that direct neurovirulence, developing therapeutics and attenuated POWV vaccines, and assessing 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 of POWV-induced encephalitis and age-dependent lethality. They established a mechanism for genetically altering POWV and generated attenuated viral mutants that fail to cause disease while eliciting protective immune responses as vaccine candidates.
Vaccines and therapeutic approaches for preventing POWV neuroinvasion are now being examined by researchers, revealing age's role in infection severity.
“Our findings provide a foundational basis for understanding neurovirulent pathogens' mechanisms in the central nervous system," Mackow explained. "They define brain senescence's role in disease severity and offer potential targeted human therapeutics that protect elderly individuals from lethal POWV infections."
The investigators detail their discovery based on the 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 adults.
Mackow stated that minimal infectious doses were highly lethal in older mice with lethality increasing more than tenfold with age. The researchers also determined that POWV lethality links to central nervous system glial cell activation and age-dependent neuroinflammatory cytokine responses, establishing mechanisms contributing to Powassan virus encephalitis.
Mackow’s research receives support from a Department of Defense (DOD) grant alongside three new National Institutes of Health grants from the National Institute of Allergy and Infectious Diseases (NIAID). The NIAID grants total $8 million over five years; combined with DOD funding, they provide approximately $9 million through August 2029.
The funded research aims to better understand mechanisms defining POWV entry into its host's brain, age-dependent responses increasing disease severity, and developing therapeutics against the virus.
___