Scientists Investigate Mechanisms of Monkeypox Virus Entry into Brain Cells

A multidisciplinary team at the University of Alberta has for the first time sought to understand how monkeypox virus may be causing neurological symptoms in people affected by the global outbreak of mpox disease, declared by the World Health Organization in 2022.

In newly published research in the journal Proceedings of the National Academy of Sciences, the team used laboratory experiments to infect human brain cells with the monkeypox virus. They found monkeypox virus infiltrated the astrocytes — a type of cell responsible for normal brain function — triggering an extreme immune response.

“Astrocytes are the most abundant neural cells in the brain,” explains first author Hajar Miranzadeh Mahabadi, a postdoctoral fellow in medicine and holder of a Canadian Institutes of Health Research HIV Trials Network fellowship. “We found that monkeypox virus can efficiently infect these cells and can induce a kind of brain cell death we call pyroptosis.”

“We were looking at the potential of the virus to infect brain cells and see what consequences that infection might have on the cells,” says co-investigator Ryan Noyce, assistant professor of medical microbiology and immunology, noting further study is required using samples from human patients, animal models and various strains of monkeypox. “Our findings shed light on the possibility of monkeypox virus infiltrating the brain and infecting cells in some instances.”

Understanding a global outbreak

More than 80,000 people had been infected by monkeypox virus by the time the outbreak was declared, according to Health Canada, and there are currently around 1,500 confirmed cases in Canada. The virus is transmitted by skin or sexual contact or respiratory droplets, and this outbreak has mainly affected men who have sex with men. Common symptoms include a rash, fever and aching muscles, but neurological symptoms such as headache, mental confusion and seizures have increasingly been observed, suggesting inflammation of brain tissue.

“The extent of monkeypox virus cases, particularly those associated with neurological complications, highlighted the urgent need to understand the potential effect of monkeypox virus in the central nervous system,” says Miranzadeh Mahabadi, noting this is the first study to examine brain cells exposed to monkeypox virus.

The research team identified a potential avenue for treatment when they were able to reduce cell death in monkeypox virus-infected cells by treating them with dimethyl fumarate, a compound approved in Europe for psoriasis and used to treat multiple sclerosis in the United States and Canada.

Noyce notes there are now two antiviral treatments approved for mpox disease and there is also a vaccine available in Canada for preventing disease in vulnerable populations.

Miranzadeh Mahabadi plans to continue her research on monkeypox and the brain, and to examine why mpox disease seems to be more severe and has a higher mortality rate among people who also have HIV.

The researchers note the study was a joint project of the laboratories of neurologist and professor of medicine Christopher Power, virologist and professor of medical microbiology and immunology David Evans, and professor of biochemistry Olivier Julien, using the U of A’s Biocontainment Level 3 facilities. Funding was provided by the Canadian Institutes of Health Research, the Canada Foundation for Innovation, the Henri M. Toupin Chair in Neurocognitive Disorders, the National Institutes of Health and The Welch Foundation. Ryan Noyce is a member of the Li Ka Shing Institute of Virology.