08:24pm Tuesday 17 October 2017

Research uncovers key difference between our bodies' fight against viruses and bacteria

The study, published in the journal Nature Immunology and led by Professor Uwe Vinkemeier in the University’s School of Life Sciences, centred on STAT1, a protein that can bind DNA and hence plays a vital role in regulating genes in the body.

STAT1 responds to interferon signals, hormone-like molecules which control communication between cells to trigger defensive action by the body’s immune system when pathogens such as bacteria, viruses, or parasites are detected. These powerful defensive actions are also part of the body’s ability to control the growth of malignant tumours that can ultimately achieve their complete elimination.

Click here for full story

It was previously thought that all interferons used single STAT1-containing units rather than STAT1 chains to regulate the activity of genes. However, using mice bred specially to express a mutated form of STAT1 which is limited to forming single STAT1 units, the Nottingham team has demonstrated that this abolishes the function of some interferons while leaving others largely unaffected.

Compromised protection

They found that when the assembly of STAT1 chains was inhibited, type I interferons responsible for protecting against viruses such as vesicular stomatitis virus were unaffected, whereas type II interferons, which protect against bacterial infections such as listeria, no longer functioned effectively.

Professor Vinkemeier said: “The core of these findings is that we are revising a central aspect of what we thought we knew about how these proteins worked. The molecular mechanisms underlying type I and type II interferon functioning are actually more distinct than we previously imagined. This in turn offers new options for rational pharmacological intervention.”

For example, type I interferons, involved in the anti-viral response also play a role in stopping cells from growing and replicating — and therefore inhibiting the spread of the virus throughout the body. These interferons are already in clinical use against Hepatitis virus and several cancers and in the treatment of auto-immune diseases like multiple sclerosis. Type-II interferon, in contrast, has been shown to be detrimental in some of these conditions, namely multiple sclerosis and melanoma, an aggressive type of skin cancer.

 

More effective treatments

“In situations like these our finding offers a new target for making current treatments more effective. There is good reason to assume that an inhibitor of STAT1 chain formation could potentially block detrimental type-II interferon responses while keeping type I activities, including anti-viral protection, intact. This would avoid an important shortcoming of current STAT1 inhibitors.”

The study was led by The University of Nottingham but involved international collaboration with researchers from Germany at the University of Göttingen Medical Centre and the Max-Planck Institute for Molecular Cell Biology and Genetics in Dresden; the Swiss Tropical and Public Health Institute in Basel, and the University of Vienna in Austria.

A copy of the paper can be found (after the embargo lifts) on the web at http://dx.doi.org/10.1038/ni.2794

— Ends —

 

Notes to editors: The University of Nottingham has 42,000 students and is ‘the nearest Britain has to a truly global university, with campuses in China and Malaysia modelled on a headquarters that is among the most attractive in Britain’ (Times Good University Guide 2014). It is also one of the most popular universities among graduate employers, one of the world’s greenest universities, and winner of the Times Higher Education Award for ‘Outstanding Contribution to Sustainable Development’. It is ranked in the World’s Top 75 universities by the QS World University Rankings.

More than 90 per cent of research at The University of Nottingham is of international quality, according to the most recent Research Assessment Exercise. The University aims to be recognised around the world for its signature contributions, especially in global food security, energy & sustainability, and health. The University won a Queen’s Anniversary Prize for Higher and Further Education for its research into global food security.

Impact: The Nottingham Campaign, its biggest ever fundraising campaign, will deliver the University’s vision to change lives, tackle global issues and shape the future. More news…

 

Story credits

More information is available from Professor Uwe Vinkemeier on +44 (0)115 823 0249, uwe.vikemeier@nottingham.ac.uk 

Emma Thorne

Emma Thorne – Media Relations Manager

Email: emma.thorne@nottingham.ac.uk Phone: +44 (0)115 951 5793 Location: University Park


Share on:
or:

Health news