An immune signaling pathway for control of Yellow Fever Virus infection

Princeton University researchers have uncovered a critical role for a new immune signaling pathway in controlling infection by the flavivirus Yellow Fever Virus (YFV), according to a paper published Aug. 15 in the journal mBio. The research stemmed from a 2015 Grand Health Challenges grant from the Princeton Environmental Institute.

Princeton University researchers have uncovered a critical role for a new immune signaling pathway in controlling infection by the flavivirus Yellow Fever Virus (YFV), according to a paper published Aug. 15 in the journal mBio. The research, led by Alexander Ploss, an assistant professor of molecular biology, stemmed from a 2015 Grand Health Challenges grant from the Princeton Environmental Institute.

Infection with YFV causes a devastating illness with a mortality rate of up to 50 percent. Like other members of its viral family — which includes West Nile Virus, Dengue virus and Zika virus — YFV is transmitted to humans by mosquitos that are expanding into new areas across the globe, exposing more people to these dangerous viruses. Fortunately, there is an effective vaccine for YFV: a live-attenuated strain of the virus, called YFV-17D, which differs by only a few amino acids from the virulent viral strain YFV-Asibi, but nonetheless provokes a potent and durable protective immune response in humans.

“An improved understanding of the complex mechanisms regulating YFV-17D attenuation will provide insights into key viral-host interactions that regulate host immune responses and infection outcomes, [and] open novel avenues for the development of innovative vaccine strategies,” said Ploss, who led the study with first author Florian Douam, a postdoctoral research associate. However, research efforts have been hampered due to the fact that mice, which are used in the study of viral infections, are resistant to YFV infection. Nonetheless, recent mouse experiments have pointed to an important role for cytokines called interferons (IFN) in controlling the virus.