Investigating the dangerous neurological effects of the Powassan virus

While Lyme disease is the most well-known and widespread tick-borne illness in the United States, other infections transmitted through tick bites can be just as, or even more, dangerous. One of these is Powassan virus (POWV). Erich Mackow, Ph.D., a virologist at Stony Brook University, is conducting research to uncover one of the most dangerous effects of POWV – neurological damage.

Powassan virus is endemic in North America. It is present in about 2% of Long Island ticks and is injected into the skin during a tick bite lasting just 15 minutes. Patients infected with POWV have a 10% risk of fatal encephalitis and up to 50% of infected patients suffer long-term neurological damage. In elderly patients, severe neurological symptoms are associated with POWV infection.

Mackow is a professor in the Department of Microbiology and Immunology at the Renaissance School of Medicine (RSOM), a core member of Stony Brook's Center for Infectious Diseases, and one of several scientists at Stony Brook University looking for ways to more specifically target tick-borne infections. Stony Brook Medicine has a clinic specializing in the treatment of 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 a mystery because the mechanisms of viral neuroinvasion are virtually unknown,” says Mackow.

As part of this research, Mackow and his colleagues at RSOM are focusing their investigations on analyzing all aspects of the neurological effects of POWV, defining viral proteins that control neurovirulence, developing therapeutics and attenuated POWV vaccines, and evaluating the role of cellular senescence—the biological process by which cells stop dividing—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 developed a mechanism to genetically modify POWV and generated attenuated virus mutants that do not cause disease and elicit protective immune responses as vaccine candidates.

Researchers are currently investigating vaccines and therapeutic approaches to prevent POWV neuroinvasion and elucidating the role of age in the severity of POWV infection.

“Our findings provide a fundamental basis for understanding the mechanisms of neurovirulent pathogens in the central nervous system, define the role of brain aging in disease severity, and demonstrate the potential to leverage responses that protect young mice from POWV lethality to develop targeted human therapeutics that protect older people from fatal POWV infections,” explains Mackow.

The researchers describe their discovery, based on the age-dependent model and new POWV genetics, in a new article published this month in the Journal of Virology.

The authors write that their laboratory results demonstrate the age-dependent lethality of POWV in a mouse model that reflects the severity of POWV in humans and the long-term central nervous system pathology in the elderly.

Mackow, the lead author, said that only minimal infectious doses of the virus were highly lethal in older mice and that lethality increased tenfold with age. The researchers also found that POWV lethality was related to activation of glial cells in the central nervous system and age-dependent neuroinflammatory cytokine responses in the mice, essentially revealing mechanisms that contribute to Powassan virus encephalitis.