Potential Dengue Fever Treating Antibody - Proved Effective for Japanese Encephalitis Viral Infections
CLEC5A is a C-type lectin expressed on the cell surface known to be a receptor which is used by the Dengue virus (DV) to attach themselves to of the host cells during infection. It also induces massive proinflammatory cytokines subsequently in an infected host. The blocking of the CLEC5A interaction with DV has been one of the research interests in Dr. Shie-Liang Hsieh’s group.
In the continuing study of CLEC5A, the team(see fig.1) has also revealed CLEC5A’s role in Japanese Encephalitis (JE), which is a viral infection caused by mosquitoes bites. Severe JE viral infection (JEV) usually is marked by quick onset, headache, high fever, neck stiffness, and all sorts of damaged neural cells related symptoms. And, there is no specific therapy for it currently.
Therefore, the study which has been published online in the PLoS Pathogens Journal at April 19th, has paved a way for a possible strategy to control neuroinflammation during viral encephalitis. JE happens more often in Asia, with up to 35,000 cases and 10,000 deaths reported each year.
According to Dr. Szu-Ting Chen, first author of this paper, their observation has led to two major findings. First of all, they have demonstrated that JEV activates macrophages and microglia via CLEC5A, and the blockade of CLEC5A can reduce bystander neuronal damage and JEV-induced proinflammatory cytokine secretion from macrophages and microglia.
Secondly, an antibody administered in-vivo to mice shows that it not only inhibits JEV-induced BBB (Blood Brain Barrier) permeability change, but also reduces the numbers of activated microglia and immune cells infiltration into the central neural system. BBB is a natural insulation to the brain so that outside infections usually are barred. Once BBB is broken, it is like open house invitations, so JEV and all kinds of immune system cells can all slip in and create chaos(see fig.2). The research has shown significant differences between JEV infected mice with and without treatment at day 7. (see fig.3) It is likely that the antibody has the effect of protecting brain cells from getting passable leakages.
This antibody is a patented drug candidate which was originally developed for Dengue fever and dengue hemorrhage fever treatment.
This paper can be found online at: http://www.plospathogens.org/article/info%3Adoi%2F10.1371%2Fjournal.ppat.1002655