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Archive - Nov 9, 2011

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Scientists Investigate “Panhandle” Structure of Salmon Virus RNA

A research team at the National Institute of Standards and Technology (NIST) has provided the first look at a genetic structure that may play a critical role in the reproduction of the infectious salmon anemia virus (ISAV), more commonly known as the "fish flu." A scourge in fish farms with a mortality rate as high as 90 percent, ISAV was recently found in wild salmon in the Pacific Northwest for the first time, threatening an already dwindling population and the vast food web it supports. The new research was published online on October 12, 2011 in the Journal of Virology. While there is a vaccine for the virus, it must be administered by injection—a task that is both cumbersome and economically impractical for the aquaculture industry. A drug or vaccine that prevents the spread of the disease by interfering with the virus' ability to replicate its genetic code (contained in eight segments of RNA) would be far more practical for fish farmers and marine biologists to deliver. Dr. Robert Brinson, a NIST scientist working at the Hollings Marine Laboratory (HML) in Charleston, South Carolina, and NIST colleagues Drs. Andrea Szakal and John Marino working at the Institute for Bioscience and Biotechnology Research (IBBR) in Rockville, Maryland, knew from the scientific literature that the family of viruses that includes both the many types of influenza—the causes of yearly human flu outbreaks—and infectious salmon anemia, form "panhandle" structures in their genomic RNA. In human influenza, these panhandles are known to interact with proteins that begin the process of copying and replicating the virus.

Proof-of-Principle for RNAi Treatment of Genetic Bone Disease

Scientists at Penn’s Perelman School of Medicine Center for Research in FOP and Related Disorders have developed a new genetic approach to specifically block the damaged copy of the gene for a rare bone disease, while leaving the normal copy untouched. Lead author Dr. Josef Kaplan, postdoctoral fellow; and senior authors Dr. Eileen M. Shore and Dr. Frederick S. Kaplan, both from the Department of Orthopaedic Surgery, published this new proof-of-principle approach for treating the disease, called FOP, online on October 20, 2011 in Gene Therapy. FOP (fibrodysplasia ossificans progressive) is a rare genetic disorder of progressive extra bone formation for which there is presently no cure. It is caused by a mutation in the gene for ACVR1/ALK2, a bone morphogenetic protein (BMP) receptor that occurs in all classically affected individuals. Individuals who have FOP harbor one normal copy and one damaged copy of the ACVR1/ALK2 gene in each cell. The mutation increases the amount of BMP in cells to greater than normal levels, which initiates the transformation of muscles and cartilage into a disabling second skeleton of bone. Using a special type of RNA molecule engineered to specifically silence the damaged copy of the gene rather than the normal copy -- a process known as RNA interference, or RNAi -- the scientists restored the cellular function caused by the FOP mutation by ridding cells of the mutant ACVR1/ALK2 mRNA. Cells were essentially left with only normal copies of ACVR1/ALK2 mRNA, thus adjusting the protein’s activity to normal, similar to that of cells without the FOP mutation. The human cells used in the experiments were adult stem cells obtained directly from discarded baby teeth donated by FOP patients.

Lipid Blocks Influenza Infection

A natural lipid in the fluid lining the lungs inhibits influenza infections in both cell cultures and mouse models, according to researchers at National Jewish Health. These findings, combined with previous studies demonstrating effectiveness against respiratory syncytial virus, suggest that the lipid molecule, known as POPG, may have broad antiviral activity. “Supplemental POPG could be an important, inexpensive, and novel approach for the prevention and treatment of influenza and other respiratory virus infections,” said Dr. Dennis Voelker, Professor of Medicine, and senior author of the report, published online on November 3, 2011 in the American Journal of Respiratory Cell and Molecular Biology. Influenza infects millions of people across the globe, killing 500,000 each year. Vaccines are highly effective, but must be reformulated each year to counter new viral strains. Two classes of drug are currently available to treat established influenza infections, although widespread resistance has developed against one class and is developing against the other. Several proteins that inhibit viral activity have been identified in the fluid lining the lungs. Until recently, however, the antiviral role of POPG (palmitoyl-oleoyl-phosphatidylglycerol) has been unknown. Previous research by Dr. Voelker, Dr. Mari Numata, and their colleagues demonstrated that POPG reduces inflammation in the lung and prevents infection by respiratory syncytial virus. In the most recent study, the researchers looked at the ability of POPG to inhibit infection by two strains of influenza, H1N1-PR8 and H3N2. They found that POPG suppressed inflammatory responses, viral propagation, and cell death normally associated with influenza infection.

Advance in Understanding the Genetics of High Blood Pressure

A researcher from the UK’s University of Leicester's Department of Cardiovascular Sciences has been involved in a ground-breaking study into the causes of high blood pressure. The study, published online on October 31, 2011 in the academic journal Hypertension, analyzed genetic material in human kidneys in a search for genes that might contribute to high blood pressure. The findings open up new avenues for future investigation into the causes of high blood pressure in humans. The study identified key genes, messenger RNAs, and micro RNAs present in the kidneys that may contribute to human hypertension. It also uncovered two microRNAs that contribute to the regulation of renin – a hormone long thought to play to part in controlling blood pressure. Although scientists have long known that the kidneys play a role in regulating blood pressure, this is the first time that key genes involved in the process have been identified through a large, comprehensive gene expression analysis of the human kidneys. It is also the first time that researchers have identified miRNAs that control the expression of the hormone renin. The scientists studied tissue samples from the kidneys of 15 male hypertensive patients and 7 male patients with normal blood pressure, and compared their messenger RNA (mRNA) and microRNA (miRNA). Messenger RNA (mRNA) is a single-stranded molecule that helps in the production of protein from DNA. Genetic information is copied from DNA to mRNA strands, which provide a template from which the cell can make new proteins. MicroRNA (miRNA) is a very small molecule that helps regulate the process of converting mRNA into proteins. The study was co-authored by the University of Leicester's Dr.

Polio Still a Threat to Public Health

Health professionals and researchers across the globe believe they are on the verge of eradicating polio, a devastating virus which can lead to paralysis and death. Despite successful eradication in most countries, there are still four countries where the virus is considered endemic -- and many more in which the virus still lurks. Dr. Lester Shulman of Tel Aviv University's Sackler Faculty of Medicine and the Israeli Ministry of Health has spent years tracking isolated cases of live poliovirus infections, often discovered in countries that are supposedly polio-free. When the live-virus version of the vaccine, called Oral Polio Vaccine (OPV) evolves, he says, it can act like wild poliovirus and continue the threat of contagion. Medical professionals widely believe that after the wild virus is eradicated, resources dedicated to polio immunization can be redirected. But this isn't so, Dr. Shulman says. He recommends that public health agencies take a three-pronged approach: vaccination policies to maintain "herd immunity" (a 95 percent immunization rate for polio) should be maintained to prevent the spread of wild and evolved vaccine strains of the virus; environmental surveillance of sewage systems should continue; and a switch to Inactivated Polio Vaccine (IPV) instead of OPV should be implemented. Dr. Shulman's research was recently published in PLoS ONE. He has also been invited as an informal expert to the World Health Organization's annual meeting on polio this fall. While the eradication of polio is seemingly within reach, this is not the time to relax, Dr. Shulman warns. Most countries only investigate the possibility of poliovirus outbreaks when paralytic cases appear in the human population. But this doesn't take into account a potential problem posed by the live virus vaccine.