A 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.
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.
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.