(Press-News.org) GALVESTON, Texas — 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
Scientists find key mechanism of childhood respiratory disease
Discovery of link between respiratory syncytial virus and oxidative stress could lead to new therapies
2011-03-08
ELSE PRESS RELEASES FROM THIS DATE:
Student innovation at Rensselaer transmits data and power wirelessly through submarine hulls
2011-03-08
Troy, N.Y. – Steel walls are no match for Tristan Lawry. The doctoral student at Rensselaer Polytechnic Institute has developed and demonstrated an innovative new system that uses ultrasound to simultaneously transmit large quantities of data and power wirelessly through thick metal walls, like the hulls of ships and submarines.
Lawry, a student in the Department of Electrical, Computer, and Systems Engineering at Rensselaer, is one of three finalists for the 2011 $30,000 Lemelson-MIT Rensselaer Student Prize. A public ceremony announcing this year's winner will be held ...
Rainwater harvest study finds roofing material affects water quality
2011-03-08
For the past few years, one of the most common questions facing the Texas Water Development Board (TWDB) hasn't been over contentious water rights or proposed water projects; it's been from homeowners wanting to know what type of roofing material is most suitable for collecting rainwater for indoor domestic use.
"Rainwater harvesting is becoming fairly widespread, at least in Central Texas. There's interest born out of necessity because people are simply running out of water in rural areas or they're interested in conserving water supplies and it's good for the environment," ...
Body's clock may lead to increased risk for fainting during the nighttime
2011-03-08
Boston, Ma – Fainting, or syncope, is quite common. About 50% of people will experience fainting at some point during their lifetime. The most common type of fainting is vasovagal syncope (VVS) that is caused by a sudden drop in blood pressure resulting in reduced blood flow to the brain. VVS can occur in healthy people due to inappropriate cardiovascular responses to certain behavioral or emotional triggers such as fear, needle prick or even standing up. VVS has a daily pattern with more occurrences during the morning. This daily pattern is possibly due to the daily distribution ...
Clinical observation leads to lung cancer discovery
2011-03-08
AURORA, Colo. (March 7, 2011) - A discovery at University of Colorado Cancer Center shows testing lung cancer on a molecular level can produce new insights into this deadly disease.
Cancer Center member D. Ross Camidge, MD, PhD, director of the thoracic oncology clinical program at University of Colorado Hospital (UCH), turned a chance clinical observation into a new field of discovery in lung cancer.
In October 2010, Camidge and colleagues published a study in the New England Journal of Medicine showing more than half of patients with a specific kind of lung cancer ...
Research demonstrates relationship of Texas coastal prairie-pothole wetlands to Galveston Bay
2011-03-08
New research reveals vast tracts of wetlands along the upper Gulf Coast are more hydrologically connected to Galveston Bay and other waters of the U.S. than previously thought, suggesting immediate implications for how they are preserved, managed and regulated, according to Texas AgriLife scientists.
"Loss of wetlands closer to traditional navigable waters must be mitigated under the Clean Water Act by creating new wetlands, or preferably by protecting and restoring similar existing wetlands," said Dr. John Jacob, Texas AgriLife Extension Service environmental quality ...
USC California superstorm would be costliest US disaster
2011-03-08
A hurricane-like superstorm expected to hit California once every 200 years would cause devastation to the state's businesses unheard of even in the Great Recession, a USC economist warns.
Researchers estimate the total property damage and business interruption costs of the massive rainstorm would be nearly $1 trillion.
USC research professor Adam Rose calculated that the lost production of goods and services alone would be $627 billion of the total over five years. Rose, a professor with the USC School of Policy, Planning, and Development, also is the coordinator for ...
Helicobacter pylori infection linked to decreased iron levels in otherwise healthy children, according to research at UTHealth
2011-03-08
HOUSTON-(March 7, 2011)- Children without previous iron deficiencies or anemia who remained infected with Helicobacter pylori (H. pylori) had significantly lower levels of iron compared to children who had the infection eradicated, according to researchers at The University of Texas Health Science Center at Houston (UTHealth).
"Half of the world's population is infected with H. pylori and most of the individuals are asymptomatically infected, according to several surveys," said Victor Cardenas, M.D., Ph.D., lead investigator of the study and associate professor of epidemiology ...
Evolution drives many plants and animals to be bigger, faster
2011-03-08
Durham, NC —For the vast majority of plants and animals, the 'bigger is better' view of evolution may not be far off the mark, says a new broad-scale study of natural selection. Organisms with bigger bodies or faster growth rates tend to live longer, mate more and produce more offspring, whether they are deer or damselflies, the authors report.
Researchers working at the National Evolutionary Synthesis Center compiled and reviewed nearly 150 published estimates of natural selection, representing more than 100 species of birds, lizards, snakes, insects and plants. The ...
People would rather let bad things happen than cause them, especially if someone is watching
2011-03-08
People are more comfortable committing sins of omission than commission—letting bad things happen rather than actively causing something bad. A new study published in Psychological Science, a journal of the Association for Psychological Science, suggests that this is because they know other people will think worse of them if they do something bad than if they let something bad happen.
"Omissions and commissions come up relatively frequently in everyday life, and we sometimes puzzle over them," says moral psychologist Peter DeScioli of Brandeis University, who conducted ...
Popular drugs for common male health problems can affect their sexual health
2011-03-08
A new study published in The Journal of Sexual Medicine reveals that, for the first time, 5a-reductase inhibitors commonly used to treat urinary problems in patients with benign prostatic hyperplasia (BPH) and found in popular medications to treat hair loss, can produce, persistent erectile dysfunction (ED), depression and loss of libido, even after the medication has been discontinued.
Researchers led by Abdulmaged M. Traish, MBA, PhD, of Boston University School of Medicine, examined data reported in various clinical studies from the available literature concerning ...
LAST 30 PRESS RELEASES:
Less intensive works best for agricultural soil
Arctic rivers project receives “national champion” designation from frontiers foundation
Computational biology paves the way for new ALS tests
Study offers new hope for babies born with opioid withdrawal syndrome
UT, Volkswagen Group of America celebrate research partnership
New Medicare program could dramatically improve affordability for cancer drugs – if patients enroll
Are ‘zombie’ skin cells harmful or helpful? The answer may be in their shapes
University of Cincinnati Cancer Center presents research at AACR 2025
Head and neck, breast, lung and survivorship studies headline Dana-Farber research at AACR Annual Meeting 2025
AACR: Researchers share promising results from MD Anderson clinical trials
New research explains why our waistlines expand in middle age
Advancements in muon detection: Taishan Antineutrino Observatory's innovative top veto tracker
Chips off the old block
Microvascular decompression combined with nerve combing for atypical trigeminal neuralgia
Cutting the complexity from digital carpentry
Lung immune cell type “quietly” controls inflammation in COVID-19
Fiscal impact of expanded Medicare coverage for GLP-1 receptor agonists to treat obesity
State and sociodemographic trends in US cigarette smoking with future projections
Young adults drive historic decline in smoking
NFCR congratulates Dr. Robert C. Bast, Jr. on receiving the AACR-Daniel D. Von Hoff Award for Outstanding Contributions to Education and Training in Cancer Research
Chimpanzee stem cells offer new insights into early embryonic development
This injected protein-like polymer helps tissues heal after a heart attack
FlexTech inaugural issue launches, pioneering interdisciplinary innovation in flexible technology
In Down syndrome mice, 40Hz light and sound improve cognition, neurogenesis, connectivity
Methyl eugenol: potential to inhibit oxidative stress, address related diseases, and its toxicological effects
A vascularized multilayer chip reveals shear stress-induced angiogenesis in diverse fluid conditions
AI helps unravel a cause of Alzheimer's disease and identify a therapeutic candidate
Coalition of Autism Scientists critiques US Department of Health and Human Services Autism Research Initiative
Structure dictates effectiveness, safety in nanomedicine
Mission accomplished for the “T2T” Hong Kong Bauhinia Genome Project
[Press-News.org] Scientists find key mechanism of childhood respiratory diseaseDiscovery of link between respiratory syncytial virus and oxidative stress could lead to new therapies