Investigators Use Experimental Flu Drug to Cure Tick-Borne Virus in Mice

Bourbon virus, a recently discovered tick-borne virus, is rare but can be deadly. The virus has only been confirmed on 3 occasions, with 2 cases resulting in death, due to a lack of specific treatments for the virus. However, a team of investigators from Washington University School of Medicine in St. Louis has successfully cured mice infected with the virus by treating the animals with an experimental antiviral flu drug.

For the research, published in the journal PLOS Pathogens, the investigators evaluated the drug favipiravir, which is approved in Japan for the treatment of influenza. This drug was selected because influenza virus is a distant cousin of Bourbon virus and favipiravir inhibits a key protein that the tick-borne virus requires for multiplication.

The research team, led by Jacco Boon, PhD, an assistant professor of medicine, were limited to conducting the study in an animal model due to the rarity of the infection in humans.

In 1 experiment the research team infected immunocompromised mice with Bourbon virus and observed that all of the mice died 6 to 8 days following infection.

In a separate experiment, the team infected mice with the virus and then treated the mice with favipiravir or placebo for the 8 days following infection. Mice who received favipiravir at the point of infection or within 1 day of infection all survived without showing signs of illness. Three days after infection with the virus the investigators administered the antiviral to mice who had already begun showing clinical signs of illness, all of which recovered following treatment. On the other hand, all of the mice that received placebo died.

"Without the flu drug, 100% of the infected mice died, and with the treatment, 100 percent survived," Boon, the paper's senior author, said in a statement. "Up until now, doctors have not had any way to treat Bourbon virus. We've found something that works, at least in mice, and it suggests that antivirals for flu are a good place to start looking for a treatment for Bourbon."

The Bourbon virus was first identified in 2014 in Kansas when a middle-aged man arrived at a hospital with flu-like symptoms and a history of tick bites. The patient was treated for ehrlichiosis, which causes similar symptoms, but his health continued to decline and diagnostic tests were unable to pinpoint a specific infection. After the man’s death a blood sample was sent to the laboratories at the US Centers for Disease Control and Prevention (CDC). CDC investigators identified the infection as a new virus, naming it Bourbon, the name of the county where the Kansas man had lived.

The virus did not manifest for another 3 years when it appeared in 2017 in the St. Louis area. A female patient presented to Barnes-Jewish Hospital and complained of fever, fatigue, and body aches. Following presentation, Jennie Kwon, DO, an infectious disease specialist and an assistant professor of medicine, at Washington University, worked alongside the CDC to identify the Bourbon virus.

Despite being able to identify the virus in the patient, the woman did not survive. This case caught the attention of Boon, who is an influenza researcher who works closely with Kwon.

"We really don't have any way of telling how common Bourbon virus infection is or how deadly it is," Boon, who is also an assistant professor of molecular microbiology, and of pathology and immunology, said in the press release. "Ticks have always been here, and now we know that Bourbon virus is in ticks in this area. There have probably always been people getting infected with Bourbon virus, and we just did not know what it was before."

A third case of Bourbon virus was identified in a patient in Oklahoma, who was able to survive the deadly virus. According to the investigators, there may have been other cases of the virus that have not resulted in hospitalization.

Despite the findings in the mouse model, the investigators are unaware whether clinicians in the United States would be able to obtain favipiravir to treat Bourbon virus as it is not approved by the US Food and Drug Administration.

For now, the best methods to protect against Bourbon virus are to avoid tick bites by using insect repellent, wearing long pants and sleeves, and conducting tick checks following outdoor activity.