Researchers identify weapon against viral infection

Experts in the US have identified how the body responds to the initial threat of viral infection, which could pave the way for more tailored therapies to be developed in the future.

Researchers at Massachusetts General Hospital (MGH) have discovered an immune cell protein called GEF-H1, which is essential to the ability of macrophages – major contributors to the innate immune system – to respond to viral infections such as influenza.

The innate immune system is the body's first line of defence against infection and rapidly responds to invading pathogens by mobilising white blood cells, chemical factors called cytokines and antimicrobial peptides.

As cells are invaded by viruses they often move towards the nucleus to replicate and often to integrate their own genetic material into that of the host cell, by traveling along microtubules that cells use for internal protein transport.

However, just how microtubule-based movement of viral components contributes to induction of the immune response has been unknown - until now.

Senior report author Dr Hans-Christian Reinecker, from the Center for the Study of Inflammatory Bowel Disease in the MGH Gastrointestinal Unit, said the findings indicate that GEF-H1 may control immune responses against a "wide variety" of RNA and DNA viruses that pose a threat to human health.

He explained that, as the team knew that GEF-H1 can bind to microtubules, their experiments led to them finding that GEF-H1 is expressed in macrophages and activated in response to viral RNA, controlling the expression of beta interferon and other cytokines.

In mouse models, those with the expression of GEF-H1 knocked out were unable to mount an effective immune response to influenza A and to encephalomyocarditis, which causes several types of infection in animals.

Dr Reinecker commented: "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 defence system."

The experts now hope that the discovery will enable the development of new strategies to curtail viral mechanisms that impede the immune responses to infections and lead to high mortality rates."