Protein that triggers immune response to viruses identified

Date: Nov-27-2013A study led by Massachusetts General Hospital in the US has identified a protein that is vital

for triggering the immune system's first response to viral infection. The researchers hope the discovery will

lead to new treatments for viruses that have evolved ways of stunting the body's immune response.

Writing in the latest online issue of Nature Immunology, the scientists describe how they found the

protein GEF-H1 plays a key role in helping macrophages - important cells in the innate immune system - react to

viral infections like influenza.

Senior author Hans-Christian Reinecker, an associate professor at Harvard Medical School, says:

"The detection of viral genetic material inside an infected cell is critical to initiating the responses

that signal the immune system to fight an infection and prevent its spread throughout the body."

Prof. Reinecker, who is also from the Center for the Study of Inflammatory Bowel Disease in the Massachusetts General Hospital Gastrointestinal Unit, explains that their findings suggest GEF-H1 may control the response of the immune

system to a range of RNA and DNA viruses that threaten human health.

Innate immune system is the first line of defense

The innate immune system is the body's first line of defense against infection. It quickly detects pathogens

and summons its foot soldiers to deal with the invasion: white blood cells, cytokines and antimicrobial

peptides.

The first thing a virus tries to do when it enters a host cell is travel to the nucleus, because this is

where it replicates - often merging its own genetic material with that of the host.

To reach the nucleus the virus travels along little tunnels called microtubules that cells use to transport

proteins. But until now, it was not clear how virus movement in microtubules affected triggering of the immune

system.

Scientists already knew that GEF-H1 binds to microtubules and that it helps the immune system recognize

bacteria.

GEF-H1 is expressed in macrophages and is triggered by viral RNA

Prof. Reinecker's lab found the protein is expressed in macrophages - key components of the innate immune

system that go around "eating" unwelcome material and pathogens. They also discovered that the

nucleic acids that make up viral RNA trigger GEF-H1, which in turn controls the expression of cytokines, such as

beta interferon.

They found mice that could not express GEF-H1 could not produce an effective immune response against two

viruses: influenza A and encephalomyocarditis, a virus that causes various inflammatory diseases in

animals.

Prof. Reinecker explains:

"The sensing of intracellular viral nucleic acids for induction of interferons is so important that many

viruses, including influenza A, have evolved specific strategies to interfere with activation of the interferon

defense system."

He adds that he and his colleagues hope the discovery will lead to new ways to foil the strategies viruses

use to prevent the immune system responding to infections.

Funds from the National Institutes of Health helped finance the study.

In October 2013, another team of US researchers reported in Cell Host & Microbe that they had also

identified a protein responsible for protection

against viral infections. They found that the protein IFITM3 can disrupt communication between two other

proteins that transport and regulate the cholesterol that many viruses need to survive.

Written by Catharine Paddock PhD

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