Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists find key mechanism of childhood respiratory disease

08.03.2011
Discovery of link between respiratory syncytial virus and oxidative stress could lead to new therapies

Researchers have identified a critical part of the process by which one of the world's most common and dangerous early childhood infections, respiratory syncytial virus, causes disease.

The discovery could lead to badly needed new therapies for RSV, which in 2005 was estimated to have caused at least 3.4 million hospitalizations and 199,000 deaths among children under five worldwide.

By analyzing samples taken from infected infants and data from laboratory-mouse experiments, University of Texas Medical Branch at Galveston scientists determined that RSV interferes with airway cells' ability to produce enzymes that keep highly damaging molecules known as reactive oxygen species under control. The virus does this by preventing the activation of a single protein needed for the expression of a variety of detoxifying enzymes. Reactive oxygen species then accumulate, causing cell-killing oxidative stress and inflammation in both infected and uninfected airway cells — a major factor in the damage done by RSV infection.

"The role of oxidative stress has been studied in everything from aging to asthma, but this is really the first study to implicate it in lung inflammation associated with viral infections," said Dr. Antonella Casola, an associate professor at UTMB Health and lead author of a paper on the research, published online March 4 in the "Articles in Press" section of the American Journal of Respiratory and Critical Care Medicine (http://ajrccm.atsjournals.org/articlesinpress.dtl). "We've been working on this project for a while — starting in cells, then moving to animal models and finally getting results in patients — so we're very excited about this paper."

The UTMB Health researchers followed up earlier studies in human cell cultures with experiments that showed a substantial reduction in the expression and activation of antioxidant enzymes in the lungs of RSV-infected mice. Further investigations revealed that mice infected by RSV had much lower levels of a protein called Nrf2 — a "transcription factor" needed to prompt the production of enzymes that clean up reactive oxygen species.

"What was really striking is that Nrf2 is a kind of master switch controlling the machinery of these antioxidant enzymes, and it appears the virus blocks its activity," said UTMB Health professor Dr. Roberto Garofalo, also a lead author on the study. "This is interesting because genetic factors have been shown to be associated with other airway diseases, and the obvious question now is do the children who develop the most severe disease in response to RSV also have an Nrf2 gene that favors a low level of expression of these antioxidant enzymes? Are we seeing a combination of two hits, one from the virus and one from genetics?"

The apparent involvement of Nrf2 also opens an intriguing therapeutic possibility, Garofalo said, because compounds that induce cells to make more of the transcription factor are already in clinical trials as potential cancer therapies. Another possibility is the delivery of short-term genetic therapy via a genetically engineered virus licensed by the National Heart, Lung and Blood Institute.

Any such intervention will have to await further human studies like the one described in the AJRCCM paper. In that part of the investigation, the researchers measured biochemical markers of reactive oxygen species and levels of antioxidant enzymes in nasal samples from 30 infants with RSV infections. The severity of the babies' disease ranged from relatively minor upper respiratory tract infections to full-blown lung disease requiring respiratory support from a ventilator.

"Our findings in patients were very consistent with what we saw in mice, " Garofalo said. "We found a significant increase in markers of oxidative injury and a significant decrease in antioxidant enzyme expression corresponding to the severity of the disease."

Because the study was conducted in a relatively small number of human subjects, Garofalo and Casola plan to conduct larger human investigations under the auspices of UTMB Health's Institute for Translational Research. In future research, they also hope to examine the possible role of other viruses in inhibiting antioxidant enzymes, produce a more detailed profile of virus-induced changes in antioxidant levels and detail the magnitude and type of oxidative damage done to airways by RSV infection.

Other authors of the American Journal of Respiratory and Critical Care Medicine paper include UTMB Health research scientist Yashoda Hosakote, allergy and immunology clinical fellows Dr. Paul Jantzi and Dr. Dana Esham, assistant professor Heidi Spratt and professor Alexander Kurosky. The National Institutes of Health, the UTMB NHLBI Proteomic Center for Airway Inflammation, the National Institute of Environmental Health Sciences, the Flight Attendant Medical Research Institute and UTMB Health's Clinical and Translational Sciences Award supported this research.

ABOUT UTMB Health: Established in 1891, Texas' first academic health center comprises four health sciences schools, three institutes for advanced study, a research enterprise that includes one of only two national laboratories dedicated to the safe study of infectious threats to human health, and a health system offering a full range of primary and specialized medical services throughout Galveston County and the Texas Gulf Coast region. UTMB Health is a component of the University of Texas System.

The University of Texas Medical Branch at Galveston
Public Affairs Office
301 University Boulevard, Suite 3.102
Galveston, Texas 77555-0144
www.utmb.edu

Jim Kelly | EurekAlert!
Further information:
http://www.utmb.edu

More articles from Health and Medicine:

nachricht Norovirus evades immune system by hiding out in rare gut cells
12.10.2017 | University of Pennsylvania School of Medicine

nachricht Flexible sensors can detect movement in GI tract
11.10.2017 | Massachusetts Institute of Technology

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Ocean atmosphere rife with microbes

17.10.2017 | Life Sciences

Neutrons observe vitamin B6-dependent enzyme activity useful for drug development

17.10.2017 | Life Sciences

NASA finds newly formed tropical storm lan over open waters

17.10.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>