UNIMAS researchers find genes that turn on JE virus

A hyperactive gene response to Japanese encephalitis virus infection ultimately leads to brain inflammation

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INVESTIGATORS from Universiti Malaya Sarawak (Unimas) have identified the specific genes that become overactive as a result of nerve cell infection with Japanese encephalitis virus. The genes activate cell receptors and signalling proteins that attract immune cells to the brain. The finding suggests that nerve cells may play a significant immune role against the virus, but may also be involved in exacerbating the brain inflammation that is characteristic of the infection.

Macro of virulent mosquitoes on human skin.Mosquitoes are carriers of malaria and Encephalitis.

Japanese encephalitis virus (JEV) is transmitted by the Culex species of mosquitoes throughout Asia and the Western Pacific, most often in rice farming regions. Most people infected show no or mild symptoms, but a small percentage develop dangerous brain inflammation, called encephalitis. About one in four cases are fatal, according to the US Centers for Disease Control and Prevention.

Cells normally respond to viral invasion by activating genes to get rid of the infection. However, little is known about the genes that are activated when neurons are infected with JEV.

“Understanding the neuronal responses to JEV infection will shed light on the interactions between the host cells and the virus,” says David Perera, a molecular biologist at the Universiti Malaysia Sarawak.

Using microarray technology, Perera, University of Malaya pathologist Wong Kum Thong, and their colleagues investigated gene expression in early and late stage JEV-infected human neuronal tumour cells.

Infected neurons showed significant changes in gene expression. Genes involved in antimicrobial responses, and cell signalling, function, maintenance, survival, and death were overexpressed in infected cells. The genes with the largest increase in expression turn on specialised pathogen-recognising cell receptors. These receptors initiate the activation and attraction of immune T cells. The genes also code for signalling proteins that regulate the T cell migration into infected neurons. A problem is that so many T cells and other protective immune cells can migrate into the neurons that severe brain inflammation ensues.

The team’s findings could contribute to improvements in the management of the disease, which currently has no treatment.

“We are hopeful that the understanding of the immune responses of infected neurons will open the door to more effective treatments,” says Perera.

Japanese encephalitis (JE) is a vector-borne zoonotic disease caused by the Japanese encephalitis virus (JEV). It causes encephalitis in human and horses, and may lead to reproductive failure in sows. The first human encephalitis case in Malaya (now Malaysia) was reported during World War II in a British prison in 1942. Later, encephalitis was observed among race horses in Singapore. In 1951, the first JEV was isolated from the brain of an encephalitis patient. The true storyline of JE exposure among humans and animals has not been documented in Malaysia. In some places such as Sarawak, JEV has been isolated from mosquitoes before an outbreak in 1992. JE is an epidemic in Malaysia except Sarawak. There are four major outbreaks reported in Pulau Langkawi (1974), Penang (1988), Perak and Negeri Sembilan (1998-1999), and Sarawak (1992). JE is considered endemic only in Sarawak. Initially, both adults and children were victims of JE in Malaysia, however, according to the current reports; JE infection is only lethal to children in Malaysia.