Yellow fever virus: new insights into the immune signalling pathways that control infection

0
Recent findings published in mBio suggest that Type III Interferon (IFN) signalling plays a critical role in preventing the viral neuroinvasion, which can occur after infection with the flavivirus Yellow Fever Virus (YFV).

Although an effective vaccine for YFV does exist, YFV-17D (a live-attenuated strain of the virus), not much is known about the viral and host factors that contribute towards this vaccine’s attenuating effect.

Study lead, Alexander Ploss from Princeton University (NJ, USA),  explained why investigating these factors is important: “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.”

In this study, researchers at Princeton University investigated the effects of infection with YFV-17D in type III receptor-deficient mice.

Researchers discovered that mice deficient in type III IFN alone were able to survive the infection, as they were able to control viral replication, which helped towards its rapid clearance from the body. However, when mice were deficient in both type I and type III receptor signalling, hyper susceptibility to YFV-17D was observed and mice eventually succumbed to the infection.

Further studies also revealed higher viral loads in the brains of type 1/type III-receptor deficient mice compared with those that were solely deficient in type III receptor signalling. This suggests that type III receptor signalling has a significant role in enhancing the susceptibility of type I receptor-deficient animals to brain infection, which ultimately increases the risk of damages to the brain such as encephalitis or spongiosis.

Also in this study, researchers correlated the high mortality observed in type I/III receptor-deficient mice with an increased permeability of the blood brain barrier, which is consistent with previous groups’ findings. However, strong imbalances were also observed in many other types of immune cells during YFV-17D infection such as impaired T-cell activation and severe alterations to the balance of proinflammatorycytokines.

Overall, these results provide strong evidence for the role of type III IFN receptor signalling in controlling YFV-17D infection.

The importance of these findings was commented on by Ploss: “We uncovered a critical role of type III IFN-mediated signaling in preserving the integrity of the blood brain barrier and preventing viral brain invasion.”

Source

Douam F, Soto Albrecht YE, Hrebikova G et al. Type III Interferon-Mediated Signaling Is Critical for Controlling Live Attenuated Yellow Fever Virus Infection In Vivo. MBio. 8(4), pii: e00819-17 (2017); https://blogs.princeton.edu/research/2017/08/15/an-immune-signaling-pathway-for-control-of-yellow-fever-virus-infection/

Share:

Leave A Comment