TIM and TAM: 2 paths used by the Dengue virus to penetrate cells

October 23, 2012

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. These works were published on line in the review "Cell Host & Microbe" of October 18, 2012.

The Dengue circulates in four different forms (four serotypes). It is transmitted to humans by mosquitoes. It is a major public health problem. 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 infection is often asymptomatic, or resembles influenza symptoms, but its most serious forms can lead to fatal haemorrhagic fevers. At present, there is no preventive vaccine or efficient antiviral treatment for these four Dengue serotypes. So it is of vital importance that we develop new therapeutic strategies.

Ali Amara's team performed genetic screening in order to identify cell receptors used by the virus to penetrate target . The researchers have determined the important function played by the TIM receptors (TIM-1, 3, 4) and TAM receptors (AXL and TYRO-3) in the penetration process of the four Dengue serotypes. Mr. Amara's team has succeeded in demonstrating that the expression of these 2 receptor families makes cells easier to infect. In addition, the researchers observed that interfering RNA or antibodies that target the TIM and TAM molecules considerably reduced the infection of the cells targeted by the . 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. Unexpectedly, the work of the Inserm researchers discovered that phosphatidylserine is abundantly expressed at the surface of virions and that it was essential that the TIM and TAM receptors recognize the phosphatidylserine to allow infection of target cells.

These results have helped to understand the first key stage in the Dengue virus infectious cycle, by discovering a new method of virus entry that works by mimicking the biological functions involved in the elimination of the apoptotic cells. The discovery of these new has also opened the way for new antiviral strategies aimed at blocking bonding of the Dengue virus with the TIM and TAM molecules.

Explore further: Human antibody for dengue virus isolated

More information: Cell Host & Microbe, 12, issue 4, October 18, 2012 doi: 10.1016/j.chom.2012.08.009

Related Stories

Human antibody for dengue virus isolated

June 22, 2012
(Phys.org) -- A group of scientists in Singapore and the UK have isolated a human antibody capable of effectively neutralizing the mosquito-borne dengue virus. Dengue fever is currently incurable and infects an estimated ...

Researchers identify Achilles heel of dengue virus, target for future vaccines

April 11, 2012
A team of scientists from the University of North Carolina at Chapel Hill and Vanderbilt University have pinpointed the region on dengue virus that is neutralized in people who overcome infection with the deadly pathogen. ...

Researchers identify new cell that attacks dengue virus

May 16, 2011
Mast cells, which can help the body respond to bacteria and pathogens, also apparently sound the alarm around viruses delivered by a mosquito bite, according to researchers at Duke-NUS Graduate Medical School in Singapore.

Recommended for you

Anti-malaria drug shows promise as Zika virus treatment

November 17, 2017
A new collaborative study led by researchers at Sanford Burnham Prebys Medical Discovery Institute (SBP) and UC San Diego School of Medicine has found that a medication used to prevent and treat malaria may also be effective ...

Decrease in sunshine, increase in Rickets

November 17, 2017
A University of Toronto student and professor have teamed up to discover that Britain's increasing cloudiness during the summer could be an important reason for the mysterious increase in Rickets among British children over ...

Scientists identify biomarkers that indicate likelihood of survival in infected patients

November 17, 2017
Scientists have identified a set of biomarkers that indicate which patients infected with the Ebola virus are most at risk of dying from the disease.

Research team unlocks secrets of Ebola

November 16, 2017
In a comprehensive and complex molecular study of blood samples from Ebola patients in Sierra Leone, published today (Nov. 16, 2017) in Cell Host and Microbe, a scientific team led by the University of Wisconsin-Madison has ...

Study raises possibility of naturally acquired immunity against Zika virus

November 16, 2017
Birth defects in babies born infected with Zika virus remain a major health concern. Now, scientists suggest the possibility that some women in high-risk Zika regions may already be protected and not know it.

A structural clue to attacking malaria's 'Achilles heel'

November 16, 2017
Researchers from The Scripps Research Institute (TSRI) and PATH's Malaria Vaccine Initiative (MVI) have shed light on how the human immune system recognizes the malaria parasite though investigation of antibodies generated ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.