New Organ Culture Model for Tick-Borne Flaviviruses

Scientists have developed a novel organ culture model to study ticks that transmit flaviviruses. This model has the potential to serve as a tool for studying tick-borne flavivirus (TBFV) biology and for screening for vaccine or drug candidates.

Jeffrey M. Grabowski, from the National Institute of Allergy and Infectious Diseases (NIAID) of the U.S. National Institutes of Health (NIH), Hamilton, Montana, and colleagues, published the results of their study online in the journal mBio.

“This tick organ culture model of TBFV infection will be useful for various applications, such as screening of tick endogenous dsRNA [double-stranded RNA] corresponding to potential control targets within midgut and salivary glands to confirm restriction of TBFV infection,” the authors write.

Tick-borne virus infections are on the rise worldwide and in the United States, said lead investigator Marshall Bloom, MD, also from the NIAID, in an interview with Contagion ^®.

Ixodid ticks serve as vectors for the TBFVs, some of which cause serious, sometimes fatal, infections in humans. Powassan virus (POWV) is the only TBFV known to circulate in North America, and causes severe meningoencephalitis. Infections with this virus are increasing and have a fatality rate of 10% to 30%, however, no licensed therapeutics or vaccines are available against POWV. In contrast, another TBFV, Langat virus (LGTV), has low neurovirulence in humans.

Although the diseases caused by these and other TBFVs are well characterized, and the infections in mammalian hosts have been reasonably well studied, Dr. Bloom stressed that one area that has been tough to study is the infection of the viruses in ticks themselves.

Most tick hosts associated with TBFVs are hard-bodied ticks such as Ixodes spp. In addition, Ixodes scapularis has been shown to be a competent vector for POWV in the laboratory. Furthermore, although LGTV has not been naturally isolated from Ixodes scapularis, this tick is also a competent experimental vector for the virus.

Therefore, Dr. Bloom’s team developed a method to more closely model virus infection in ticks than is possible simply by using tick cell cultures. They achieved this by culturing organs (midgut, salivary glands, and nervous tissue) dissected from Ixodes scapularis ticks, and then infecting these organ cultures with flaviviruses and evaluating virus viability over several days.

“The work we published demonstrates that important organs dissected from living ticks could be cultured ex vivo and be viable for longer than one week,” said Dr. Bloom. “In addition, we demonstrated by several methods that viruses not only infect these organs, but can spread.”

He and his team found that the dissected organs were metabolically active for 9 to 10 days. They also found that LGTV and POWV were able not only to replicate in these organ cultures, but also to spread within the salivary glands and midgut.

“This information will enable us to look with great precision at the type of cells in the tick midgut and salivary gland that virus is actually infecting,” Dr. Bloom concluded. “It may also enable us to identify countermeasures that would be useful in combating tick-borne virus infections in ticks.”

Dr. Parry graduated from the University of Liverpool, England in 1997 and is a board-certified veterinary pathologist. After 13 years working in academia, she founded Midwest Veterinary Pathology, LLC where she now works as a private consultant. She is passionate about veterinary education and serves on the Indiana Veterinary Medical Association’s Continuing Education Committee. She regularly writes continuing education articles for veterinary organizations and journals, and has also served on the American College of Veterinary Pathologists’ Examination Committee and Education Committee.