Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Your genes may hold key to how sick you get from the flu

06.11.2006
With lessons from the 1918 flu pandemic in the rearview mirror and the avian flu a looming obstacle in the road ahead, researchers from Southern Illinois University School of Medicine are trying to understand why a flu virus kills some people but not others.

With the help of some high tech equipment, well-defined mouse models and lots of analytical know how, physiologists are beginning to hone in on the secret to this differential response. It’s probably in the genes – and the proteins they encode.

Two studies to be presented at The American Physiological Society conference “Physiological Genomics and Proteomics of Lung Disease” have found that a strain of mice that is more likely to die of influenza infection mounts a dramatically enhanced immune response in the lungs compared to a strain of mice that generally develops milder disease.

The long-term goal of these studies is to identify genes that control the individual variation in inflammation during influenza infection. This information could ultimately help identify those most at risk to develop severe disease and die from the flu, and help doctors direct vaccines, anti-viral and anti-inflammatory medications to those who need them most.

The researchers will present the study “Inflammatory responses in inbred mice with different susceptibility phenotypes to Influenza A virus infection,” on Nov. 3. The study was carried out by Rita Trammell and Linda Toth of the Southern Illinois University School of Medicine, Springfield, Ill. The conference takes place Nov. 2-5 in Fort Lauderdale.

Lessons from 1918

“Flu epidemics typically kill the very old and the very young. But the 1918 epidemic killed millions around the world, including many healthy young adults. The healthy immune systems of young adults produced an overly strong immune response that resulted in severe inflammation of the lungs. Similar to the 1918 pandemic virus, most H5N1 avian influenza virus infections occur in young adults with no pre-existing medical conditions,” Trammell noted.

“The recent emergence of the highly pathogenic H5N1 influenza virus has raised international concerns that continued evolution of the virus could cause a pandemic with global health and economic consequences,” Trammell said. “Should this occur, the ability to identify those at highest risk for developing severe disease may help to determine who would benefit most if vaccines and anti-viral therapeutics are in limited supply,” she said.

“Studies to date have focused on the virus itself to determine what makes some viruses killers,” she said. “Our research looks at the role of the host’s genetic background, an area that has remained largely unexplored.”

Flu fells some, not others

Trammell and Toth infected two strains of laboratory mice with an Influenza A virus. “Our previous studies established that if you give the same dose of influenza A virus to both strains of mice, about half of the BALB/cByJ (Type B) mice will die, compared to about 10% of the C57BL/6J (Type C) mice,” Trammell said.

The researchers studied the early immune response by examining the lung tissues of mice 30 hours after they were infected. They measured the amount of virus, cytokines and myeloperoxidase that was present in the lungs.

Cytokines and myeloperoxidase are proteins that function in the immune response. Some cytokines are pro-inflammatory, that is, they cause inflammation that helps to eliminate the pathogen. In a well-orchestrated immune response, pro-inflammatory cytokines act first and then recede once the virus is eliminated. Anti-inflammatory cytokines regulate the immune response to minimize damage to normal tissues. Myeloperoxidase is an enzyme that indicates the number of neutrophils -- a type of white blood cell -- present in the lung.

Inflammation of lungs is the difference

The researchers found the level of virus in the lungs of the two mouse strains did not differ significantly. However, all the pro-inflammatory cytokines, with one exception, were significantly higher in the Type B (disease susceptible) mice when compared to Type C (disease resistant) mice.

“Although viral titers are equivalent, B mice develop a much greater pro-inflammatory response during influenza infection than C mice, which may contribute to the differential mortality in these strains,” the authors concluded.

A related study, “Microarray analysis of gene expression in the lungs of influenza-infected C57BL/6J and BALB/cByJ mice,” complemented these findings. In this study, Toth and fellow Southern Illinois University School of Medicine researcher, Ming Ding, examined what happened to immune-related messenger RNA (mRNA) levels after the two mouse strains were exposed to the flu. The immune-related mRNAs evaluated in this study ultimately produce the proteins important to the immune response.

Like the other study, these researchers found no difference in the amount of virus in the lungs of the two mouse strains after influenza infection. But they were “amazed at the difference in immune-related mRNA levels between the two strains,” Trammell said. When compared to uninfected control mice, the mRNA levels in Type B mice were on average 24 times higher, with some types of mRNA increasing more than 100 fold. In contrast, mRNA levels in Type C mice only increased less than 3-fold after infection.

“Both studies show clear and dramatic differences in the pulmonary inflammatory response of the Type B strain of mice, as compared with Type C strain, after infection with the same dose of influenza virus,” Trammell said. “These distinctive responses to the identical virus challenge suggest that the genetic control of the inflammatory response differs between these two strains.”

Toth and Ming will present their study at the conference on Nov 3.

“Our long-term goal is to identify genomic regions, genes, and alleles that control variation in inflammation during infection with influenza virus,” Trammell said. “The identification of these genomic regions has enormous implications for understanding and avoiding the fatality associated with infection.”

These studies are at the cutting edge of proteomic and genomic research, which has taken a big leap with recent advances in imaging technology and new methods of analyzing masses of data.

Funding

The research was funded by the National Institutes of Health.

Christine Guilfoy | EurekAlert!
Further information:
http://www.the-aps.org

Further reports about: Influenza Trammell cytokines flu immune response inflammation mRNA pro-inflammatory strain

More articles from Life Sciences:

nachricht Link Discovered between Immune System, Brain Structure and Memory
26.04.2017 | Universität Basel

nachricht Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

Millions through license revenues

27.04.2017 | Health and Medicine

The TU Ilmenau develops tomorrow’s chip technology today

27.04.2017 | Information Technology

Scientist invents way to trigger artificial photosynthesis to clean air

26.04.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>