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Scientists discover how dengue virus enters human cells

Scientists discover how dengue virus enters human cells

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London:  Scientists have discovered two families of receptors that play an important role in the penetration of the dengue into human cells, paving way for a new therapy to combat the deadly virus.

These results have helped to understand the first key stage in the dengue virus infectious cycle, by discovering a new method of its entry by mimicking the biological functions involved in the elimination of the apoptotic cells, or programmed cell death, researchers said.

The study led by Ali Amara at the combined Inserm/CNRS-Universite Paris Diderot performed genetic screening in order to identify cell receptors used by the virus to penetrate target cells.

By demonstrating that it is possible to inhibit the viral infection in vitro by blocking the bonding between the virus and these receptors, the researchers have opened the way to a new antiviral strategy.

Researchers determined the important function played by the TIM and TAM receptors in the penetration process of the four Dengue serotypes.

Amara's team succeeded in demonstrating that expression of these receptor families makes cells easier to infect.

Researchers observed that interfering RNA or antibodies that target the TIM and TAM molecules considerably reduced the infection of the cells targeted by the dengue virus.

The TIM and TAM molecules belong to two distinct families of transmembrane receptors that interact either directly (TIM) or indirectly (TAM) with phosphatidylserine, an "eat-me" signal that allows the phagocytosis and the elimination of these apoptopic cells.

Researchers discovered that phosphatidylserine is abundantly expressed at the surface of virions and that it was essential that the TIM and TAM receptors recognise it to allow infection of target cells.

The discovery of these new receptors has also opened the way for new antiviral strategies aimed at blocking bonding of the Dengue virus with the TIM and TAM molecules.

The dengue virus circulates in four different forms (four serotypes). It is transmitted to humans by mosquitoes.

Two billion people throughout the world are exposed to the risk of infection and 50 million cases of dengue fever are recorded by the WHO every year, the report said.

The number of dengue cases in New Delhi has touched 720 this year. The capital saw 572 cases of dengue, including eight originating from outside, and four deaths last year.

The infection is often asymptomatic, or resembles influenza symptoms, but its most serious forms can lead to fatal haemorrhagic fevers, it said.

At present, there is no preventive vaccine or efficient antiviral treatment for these four dengue serotypes. The study was published in the journal Cell Host and Microbe.

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