Memphis, Tenn. Studies at Le Bonheur Children's Hospital in Memphis, Tenn., are advancing our understanding of how viruses, including RSV, replicate in humans, mutate to avoid the immune response and can be effectively treated.
John DeVincenzo, MD, medical director of Molecular Diagnostics and Virology Laboratories at Le Bonheur, and professor of Pediatrics and Microbiology, Immunology, and Molecular Biology at The University of Tennessee Health Science Center, has recently published three papers on this topic. DeVincenzo's lab is one of only two of its kind in the United States. His work has focused on respiratory syncytial virus (RSV), the most common cause of infant hospitalization, and his findings are leading the way towards the development of antiviral treatment strategies against the disease.
Summaries of the studies' findings include:
Complete viral RNA genome sequencing of ultra-low copy samples by sequence-independent amplification. Nucleic Acids Research, 2012
Viruses change and mutate at rapid rates in virtually random fashion. These high mutation rates of viruses always occur while they replicate within their human hosts. Detecting these changes has been difficult, because mutations that do not help the virus survive and replicate are overwhelmed by mutations that do help. Therefore, it is necessary to be able to detect minute populations of viruses that have mutated and to differentiate these small subpopulations from the majority populations of these viruses. This study outlines new advanced methods and techniques to detect minute sub-populations of viruses within clinical samples obtained from humans. These new techniques can open up areas of research in these viruses and how they mutate to avoid detection and control by our immune systems. Researchers capture 96 to 100 percent of the viral protein-coding region of HIV, respiratory syncytial and West Nile viral samples from as few as 100 copies of viral RNA. Methods are scalable to large numbers of samples and capable of generating full or near full-length viral genomes from clone and clinical samples with low amounts of viral RNA, without prior sequence information and in the presence of substantial RNA contamination from the surrounding human cells.
Assessing modeled CO2 retention and rebreathing of a facemask designed for efficient delivery of aerosols to infants. International Scholarly Research Network, 2012
New medicines for infant lung diseases, such as RSV, might require deposition of these medicines directly into the lung by infants breathing an aerosol. However, efficient masks that allow the safe delivery of these aerosols without causing the infants to re-breathe their own exhaled CO2 have not previously been developed. The researchers developed a new infant aerosol delivery mask. They then evaluated the mask using computational fluid dynamic models to see if it would both efficiently deliver aerosols and whether there was retention of exhaled CO2. Because RSV (respiratory syncytial virus) primarily is an infant disease, this device could be used for delivery of aerosol treatments of RSV in infants and children.
The promise and progress of RNA interference-based antiviral therapy for respiratory viruses. Antiviral Therapy, 2012
In this invited review, DeVincenzo discusses the science behind RNA interference (RNAi) and the potential practical issues in applying this novel treatment technology against various respiratory viral diseases. DeVincenzo was the first to demonstrate that RNAi-based therapies could work in humans. One of his recent studies showed that RSV-infected lung transplant patients treated with the novel RNAi therapy improved long term lung function significantly better than did those treated with placebo, even when the patients were analyzed as long as six months later. This marks the first effective treatment of RSV in this vulnerable immune-suppressed population. Ongoing research directed by DeVincenzo is now moving experimental RSV therapies into children.
|Contact: Hillary Welton|
Le Bonheur Children's Hospital