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 A Map of the Cell’s Power Station
18.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

nachricht On the way to developing a new active ingredient against chronic infections
18.08.2017 | Deutsches Zentrum für Infektionsforschung

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fizzy soda water could be key to clean manufacture of flat wonder material: Graphene

Whether you call it effervescent, fizzy, or sparkling, carbonated water is making a comeback as a beverage. Aside from quenching thirst, researchers at the University of Illinois at Urbana-Champaign have discovered a new use for these "bubbly" concoctions that will have major impact on the manufacturer of the world's thinnest, flattest, and one most useful materials -- graphene.

As graphene's popularity grows as an advanced "wonder" material, the speed and quality at which it can be manufactured will be paramount. With that in mind,...

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

A Map of the Cell’s Power Station

18.08.2017 | Life Sciences

Engineering team images tiny quasicrystals as they form

18.08.2017 | Physics and Astronomy

Researchers printed graphene-like materials with inkjet

18.08.2017 | Materials Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>