Japanese Encephalitis Antibodies, Proteins & ELISA Kits

Japanese encephalitis (JE) is an infectious disease caused by the zoonotic mosquito-borne Flavivirus called Japanese encephalitis virus (JEV). JE is endemic in regions of Asia and the Pacific and the main vector of transmission is the Culex species.

While many people are asymptomatic for JE, the people who become symptomatic after acquiring the infection suffer significant morbidity and mortality. Some common symptoms are headaches, fever, coma, cerebral inflammation and tremors. 30-50% of encephalitis survivors also experience cognitive, psychiatric and neurologic complications following infection.

According to the World Health Organization (WHO) there are 68,000 clinical cases of JE observed annually with up to 13,600-20,400 resulting in mortality. There are four main types of vaccines which are approved for use in humans at present and one example is the cell culture-derived killed inactivated vaccine, marketed as IXIARO®. While the number of cases of JE have depleted over the years, there is the need for further research in order to enhance and develop JE vaccines.

JEV has capsid (C) proteins, envelope (E) proteins and pre-membrane (prM) proteins which play a variety of roles in mechanisms such as viral attachment, host penetration, immune evasion and viral pathogenesis. As well as this, JEV has nonstructural proteins such as NS1, NS2a, NS2b, NS3, N4a, NS4b and NS5. Assay Genie provides a JEV recombinant protein which can be used extensively for research purposes and vaccine development.

Understanding what host receptors bind to JEV antigens and cause the induction of signaling pathways can aid in JE vaccine development. It has been shown that toll-like receptor 2 (TLR2), TLR3 and TLR7 are all involved in mediating an immune response against JEV. Retinoic-acid-inducible protein I (RIG-I) and C-type lectin domain family 5 member A (CLEC5A) receptors also bind to JEV. In particular, RIG-I is important for the production of interferons in response to JE infections and CLEC5A binding to JEV leads to the phosphorylation of DNAX activation protein in macrophages.

As well as this, infection with JEV activates the NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome when the nucleotide-binding and oligomerization domain (NOD)-like receptor NLRP3 recognizes pathogen-associated molecular patterns (PAMPs) of JEV.

Immunometabolism is an important area of science which encompasses regions of metabolism and immunology. Many of the functional capacities of immune cells are dependent on the metabolic state of the cell and its capability to mount an immune response. JEV targets the mitochondria and alters oxidative phosphorylation (OXPHOS) during viral growth and replication. In particular, researchers have observed a down-regulation of ATP synthase ATP5B which reduces energy production by OXPHOS and there is the production of reactive oxygen species (ROS).

As well as this, JE infections leads to the reduction of adenosine triphosphate (ATP) levels through glycolysis and the citric acid (TCA) cycle. Research has shown that JEV causes the alteration of host metabolic machinery whereby there is a decline in metabolic enzymes levels such as glyceraldehyde 3 phosphate dehydrogenase (GAPDH), enolase, pyruvate dehydrogenase, lactate dehydrogenase and isocitrate dehydrogenase.

It is important to better understand the host immune response to JEV in order to develop more efficacious vaccines against the virus and enhance current ones. During neurotropic viral infections there is viral passage across the blood brain barrier (BBB) and entry into the brain. In particular in JEV infections, the tight junctions between endothelial cells often become leaky due to the pro-inflammatory response, which enables JEV to cross the BBB.

During the inflammatory response in JEV infections, there is an increase in cytokine and chemokine levels in comparison to uninfected individuals. These include interferon-alpha (IFN-alpha), IFN-beta, IFN-gamma, tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), IL-1beta, IL-8 (CXCL8), CCL5 (RANTES), monocyte chemoattractant protein-1 (MCP-1/CCL2) and CXCL10 (IP-10).

Animal models are useful research tools which are often used in early stages of therapeutic product development and pathogenesis studies. JEV infection studies have been conducted in numerous animal models such as rabbits, guinea pigs, monkeys, hamsters, rats and mice. For example, JEV pathogenesis studies in golden hamster models have been performed in order to evaluate if there is cross-protective immunity if a hamster is inoculated with other Flavivirus species like West Nile Virus. As well as this, JEV causes rhesus monkeys to develop symptoms similar to the ones observed in humans, such as weakness, tremors, encephalitis and death in extreme cases.

JEV, Yellow Fever Virus, West Nile Virus, Zika virus, Tick-borne encephalitis and Dengue belong to the genus Flavivirus. Many studies have identified structural and genetic similarities between the Flavivirus viruses. Studying components of these global health threats can aid in JEV therapeutic and vaccine research.

• West Nile Virus
• Yellow Fever Virus
• Zika Virus