Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Genetics of flu susceptibility

Researchers find gene that can transform mild influenza to a life-threatening disease

A genetic finding could help explain why influenza becomes a life-threating disease to some people while it has only mild effects in others. New research led by the Wellcome Trust Sanger Institute has identified for the first time a human gene that influences how we respond to influenza infection.

People who carry a particular variant of a gene called IFITM3 are significantly more likely to be hospitalised when they fall ill with influenza than those who carry other variants, the team found. This gene plays a critical role in protecting the body against infection with influenza and a rare version of it appears to make people more susceptible to severe forms of the disease. The results are published in the journal Nature.

A central question about viruses is why some people suffer badly from an infection and others do not. IFITM3 is an important protein that protects cells against virus infection and is thought to play a critical role in the immune system's response against such viruses as H1N1 pandemic influenza, commonly known as 'swine flu'. When the protein is present in large quantities, the spread of the virus in lungs is hindered, but if the protein is defective or absent, the virus can spread more easily, causing severe disease.

"Although this protein is extremely important in limiting the spread of viruses in cells, little is known about how it works in lungs," explains Aaron Everitt, first author from the Wellcome Trust Sanger Institute. "Our research plays a fundamental part in explaining how both the gene and protein are linked to viral susceptibility."

The antiviral role of IFITM3 in humans was first suggested by studies using a genetic screen, which showed that the protein blocked the growth of influenza virus and dengue virus in cells. This led the team to ask whether IFITM3 protected mice from viral infections. They removed the IFITM3 gene in mice and found that once they contracted influenza, the symptoms became much more severe compared to mice with IFITM3. In effect, they found the loss of this single gene in mice can turn a mild case of influenza into a fatal infection.

The researchers then sequenced the IFITM3 genes of 53 patients hospitalised with influenza and found that some have a genetic mutant form of IFITM3, which is rare in normal people. This variant gene encodes a shortened version of the protein which makes cells more susceptible to viral infection.

"Since IFITM3 appears to be a first line defender against infection, our efforts suggest that individuals and populations with less IFITM3 activity may be at increased risk during a pandemic and that IFITM3 could be vital for defending human populations against other viruses such as avian influenza virus and dengue virus" says Dr. Abraham Brass, co-senior author and Assistant Professor at the Ragon Institute and Gastrointestinal Unit of Massachusetts General Hospital.

This research was a collaboration between institutes in the United States and the United Kingdom. The samples for this study were obtained from the MOSAIC consortium in England and Scotland, co-ordinated from the Centre for Respiratory Infection (CRI) at Imperial College London, and the GenISIS consortium in Scotland at the Roslin Institute of the University of Edinburgh. These were pivotal for the human genetics component of the work.

"Collectively, these data reveal that the action of a single antiviral protein, IFITM3, can profoundly alter the course of the flu and potentially other viruses in both human and mouse," explains Professor Paul Kellam, co-senior author from the Wellcome Trust Sanger Institute. "To fully understand how both the protein and gene control our susceptibility to viral infections, we need to study the mechanisms of the gene variant more closely.

"Our research is important for people who have this variant as we predict their immune defences could be weakened to some virus infections. Ultimately as we learn more about the genetics of susceptibility to viruses, then people can take informed precautions, such as vaccination to prevent infection."

Sir Mark Walport, director of the Wellcome Trust, said: "During the recent swine flu pandemic, many people found it remarkable that the same virus could provoke only mild symptoms in most people, while, more rarely, threatening the lives of others. This discovery points to a piece of the explanation: genetic variations affect the way in which different people respond to infection.

"This important research adds to a growing scientific understanding that genetic factors affect the course of disease in more than one way. Genetic variations in a virus can increase its virulence, but genetic variations in that virus's host – us – matter greatly as well."

Notes to Editors

Additional quotes

"This new discovery is the first clue from our detailed study of the devastating effects of flu in hospitalised patients", said Professor Peter Openshaw, the CRI's Director. "It vindicates our conviction that there is something unusual about these patients, and that ground-breaking clinical studies can be performed in the UK".
Professor David Hume, Director of The Roslin Institute and author on the study, says: "This work contributes greatly to our understanding of the reasons why susceptibility to serious infectious disease is so highly heritable. It is a study that couldn't have happened without the contribution of the patients of the GenISIS consortium in Scotland and the MOSAIC consortium in England and Scotland. We are extremely grateful for their support."

Publication Details

Everitt et al 'IFITM3 restricts the morbidity and mortality associated with influenza' Published on Nature online on 25 March 2012 doi:10.1038/nature10921

This work was supported by the Wellcome Trust. The MOSAIC work was supported by Imperial's National Institute for Health Research Comprehensive Biomedical Research Centre (cBRC) , the Wellcome Trust and Medical Research Council UK. The GenISIS work was supported by the Chief Scientist Office (Scotland). A.L.B. is the recipient of a Charles H. Hood Foundation Child Health Research Award, and is supported by grants from the Phillip T. and Susan M. Ragon Institute Foundation, the Bill and Melinda Gates Foundation's Global Health Program and the National Institute of Allergy and Infectious Diseases. J.K.B. is supported by a Wellcome Trust Clinical Lectureship through the Edinburgh Clinical Academic Track (ECAT).
Participating Centres

A full list of participating centres can be found at the Nature Genetics website.

Selected Websites

The Wellcome Trust Sanger Institute is one of the world's leading genome centres. Through its ability to conduct research at scale, it is able to engage in bold and long-term exploratory projects that are designed to influence and empower medical science globally. Institute research findings, generated through its own research programmes and through its leading role in international consortia, are being used to develop new diagnostics and treatments for human disease.

Imperial College London consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.

Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve global health, tackle climate change, develop sustainable sources of energy and address security challenges.

In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK's first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.

The Wellcome Trust is a global charitable foundation dedicated to achieving extraordinary improvements in human and animal health. We support the brightest minds in biomedical research and the medical humanities. Our breadth of support includes public engagement, education and the application of research to improve health. We are independent of both political and commercial interests.

Aileen Sheehy | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>