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Toll-like Receptor (Tlr3) Attachment Leads To Lethal Encephalitis

Researchers have found that recognisation of West Nile Virus (WNV) by Toll-like// receptor (Tlr3) as the major factor which allows the virus to cross the blood-brain barrier (BBB) and cause lethal encephalitis.

WNV is a single stranded RNA (ssRNA) flavivirus with a life cycle that primarily involves birds and mosquitoes; however, humans and horses can become infected. In humans, infection is generally asymptomatic and if West Nile fever does develop then the illness is generally mild and self limiting. In elderly and immunocompromised individuals, however, WNV infection can progress to severe neurological disease. The molecular details oft he pathogenesis of severe disease are scarce. It is know that some TLRs can detect viral motifs such as ssRNA. In this study, researchers investigated the role of one of these TLRs , Tlr3, in the detection of WNV using a mouse model of WNV encephalitis.

Initial investigation showed that following intraperitonially challenge with a lethal dose of WNV, Tlr3 mice were more resistant to infection than wild type mice. Quantitative PCR assays showed that, following this challenge, the viral burden in the peripheral blood was increased in Tlr3 mice compared with wild type mice. Analysis blood cytokine levels showed increased levels of inflammatory cytokines in wild type, compared with Tlr3 mice early in infection. The results indicate that Tlr3 did have a role in WNV entry in to the brain. This was confirmed by comparing the permeability of BBB in wild type and Tlr3 mice following WNV infection or stimulation with the viral mimic poly (I:C), the permeability was increased in wild type mice but not in Tlr3 mice. A further insight into the pathogenesis of severe disease was provided by results suggesting that TNF-a receptor I signaling downstream of Tlr3 promotes WNV entry into the brain. Sporadic outbreaks of WNV infection of humans have become increasingly common over the past 5 years, particularly in North America and Europe. This new work identifying Tlr3 as the receptor allowing WNV to enter the brain can hopefully be exploited for the development of new therapeutics.

Source: Nature Microbiology.

Related Information on Mosquito borne infections in Medindia:

In India, malaria, filaria and dengue are the most prevalent diseases spread by mosquitoes. Over two million cases of malaria alone are reported. Even more astonishing is the fact that India spends 100 million dollars on malaria. In spite of spending so much, the diseases continue to explode from time to time. The reason is that these mosquitoes develop resistance to medicines and chemicals.

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