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 such infection is the Powassan virus (POWV). Erich Mackow, PhD, a virologist at Stony Brook University, is researching the neurological damage caused by POWV.
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 a 15-minute tick bite. Patients infected with POWV have a 10 percent risk of fatal encephalitis and up to 50 percent may suffer long-term neurological damage. Severe symptoms are more common in older patients.
Mackow is a professor in the Department of Microbiology and Immunology at 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 treatments for tick-borne infections. Stony Brook Medicine has a clinic dedicated to treating Lyme disease and other tick-borne infections like POWV and houses 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.
Mackow and his RSOM colleagues are analyzing all aspects of POWV's neurological effects, defining viral proteins that direct neurovirulence, developing therapeutics and attenuated vaccines, and assessing cell senescence as an age-dependent cause of POWV encephalitis.
The team isolated a Powassan virus strain from ticks on Long Island and developed an animal model showing age-dependent lethality from POWV-induced encephalitis. They established a mechanism for genetically altering POWV and generated attenuated viral mutants that serve as vaccine candidates without causing disease but eliciting 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, define the role of brain senescence in disease severity, and [highlight] potential responses that protect young mice from POWV lethality to develop targeted human therapeutics that protect [the] elderly from lethal POWV infections,” explains Mackow.
The investigators detail their discovery based on an age-dependent model and novel genetics in a new paper published this month in 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 stated that minimal infectious doses were highly lethal in older mice with lethality increasing over tenfold with age. Researchers also determined that lethality is linked to central nervous system glial cell activation and age-dependent neuroinflammatory cytokine responses contributing to Powassan virus encephalitis.
Ongoing research supported by $9 million in grant funding
Mackow’s research receives support from a Department of Defense (DOD) grant along with three new National Institutes of Health grants from 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 behind POWV entry into host brains, age-dependent responses increasing disease severity, and development of therapeutics and vaccines against this virus.