New Chinese herbal medicine has significant potential in treating hepatitis C, study suggests

ata from a late-breaking abstract presented at the International Liver CongressTM 2014 identifies a new compound, SBEL1, that has the ability to inhibit hepatitis C virus (HCV) activity in cells at several points in the virus’ lifecycle.[i]SBEL1 is a compound isolated from Chinese herbal medicines that was found to inhibit HCV activity by approximately 90%. SBEL1 is extracted from a herb found in certain regions of Taiwan and Southern China. In Chinese medicine, it is used to treat sore throats and inflammations. The function of SBEL1 within the plant is unknown and its role and origins are currently being investigated.Scientists pre-treated human liver cells in vitro with SBEL1 prior to HCV infection and found that SBEL1 pre-treated cells contained 23 percent less HCV protein than the control, suggesting that SBEL1 blocks virus entry. The liver cells transfected with an HCV internal ribosome entry site (IRES)-driven luciferase reporter that were treated with SBEL1 reduced reporter activity by 50% compared to control. This suggests that that SBEL1 inhibits IRES-mediated translation, a critical process for viral protein production.In addition, the HCV ribonucleic acid (RNA) levels were significantly reduced by 78 percent in HCV infected cells treated with SBEL1 compared to the control group. This demonstrates that SBEL1 may also affect the viral RNA replication process.Prof. Markus Peck-Radosavljevic, Secretary-General of the European Association for the Study of the Liver and Associate Professor of Medicine, University of Vienna, Austria, commented: “People infected with hepatitis C are at risk of developing severe liver damage including liver cancer and cirrhosis. In the past, less than 20 percent of all HCV patients were treated because the available treatments were unsuitable due to poor efficacy and high toxicity. Recent advances means that we can now virtually cure HCV without unpleasant side effects. …

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Regenerating orthopedic tissues within the human body

By combining a synthetic scaffolding material with gene delivery techniques, researchers at Duke University are getting closer to being able to generate replacement cartilage where it’s needed in the body.Performing tissue repair with stem cells typically requires applying copious amounts of growth factor proteins — a task that is very expensive and becomes challenging once the developing material is implanted within a body. In a new study, however, Duke researchers found a way around this limitation by genetically altering the stem cells to make the necessary growth factors all on their own.They incorporated viruses used to deliver gene therapy to the stem cells into a synthetic material that serves as a template for tissue growth. The resulting material is like a computer; the scaffold provides the hardware and the virus provides the software that programs the stem cells to produce the desired tissue.The study appears online the week of Feb. 17 in the Proceedings of the National Academy of Sciences.Farshid Guilak, director of orthopaedic research at Duke University Medical Center, has spent years developing biodegradable synthetic scaffolding that mimics the mechanical properties of cartilage. One challenge he and all biomedical researchers face is getting stem cells to form cartilage within and around the scaffolding, especially after it is implanted into a living being.The traditional approach has been to introduce growth factor proteins, which signal the stem cells to differentiate into cartilage. Once the process is under way, the growing cartilage can be implanted where needed.”But a major limitation in engineering tissue replacements has been the difficulty in delivering growth factors to the stem cells once they are implanted in the body,” said Guilak, who is also a professor in Duke’s Department of Biomedical Engineering. “There’s a limited amount of growth factor that you can put into the scaffolding, and once it’s released, it’s all gone. We need a method for long-term delivery of growth factors, and that’s where the gene therapy comes in.”For ideas on how to solve this problem, Guilak turned to his colleague Charles Gersbach, an assistant professor of biomedical engineering and an expert in gene therapy. Gersbach proposed introducing new genes into the stem cells so that they produce the necessary growth factors themselves.But the conventional methods for gene therapy are complex and difficult to translate into a strategy that would be feasible as a commercial product.This type of gene therapy generally requires gathering stem cells, modifying them with a virus that transfers the new genes, culturing the resulting genetically altered stem cells until they reach a critical mass, applying them to the synthetic cartilage scaffolding and, finally, implanting it into the body.”There are a few challenges with that process, one of them being that there are way too many extra steps,” said Gersbach. “So we turned to a technique I had previously developed that affixes the viruses that deliver the new genes onto a material’s surface.”The new study uses Gersbach’s technique — dubbed biomaterial-mediated gene delivery — to induce the stem cells placed on Guilak’s synthetic cartilage scaffolding to produce growth factor proteins. …

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New RNA interference technique finds seven genes for head and neck cancer

In the hunt for genetic mutations that cause cancer, there is a lot of white noise. So although genetic sequencing has identified hundreds of genetic alterations linked to tumors, it’s still an enormous challenge to figure out which ones are actually responsible for the growth and metastasis of cancer. Scientists in Rockefeller’s Laboratory of Mammalian Cell Biology and Development have created a new technique that can weed out that noise — eliminating the random bystander genes and identifying the ones that are critical for cancer. Applying their technique to head and neck cancers, they’ve discovered seven new tumor-suppressor genes whose role in cancer was previously unknown.The new technique, which the lab recently applied to a screen for skin tumor genes, is particularly useful because it takes a fraction of the resources and much less time than the traditional method for determining gene function — breeding genetically modified animals to study the impact of missing genes.”Using knockout mice, which are model organisms bred to have a particular gene missing, is not feasible when there are 800 potential head and neck cancer genes to sort through,” says Daniel Schramek, a postdoctoral fellow in the lab, which is headed by Rebecca C. Lancefield Professor Elaine Fuchs. “It can take about two years per gene. Our method can assess about 300 genes in a single mouse, in as little as five weeks.”The researchers made use of RNA interference, a natural process whereby RNA molecules inhibit gene expression. They took short pieces of RNA which are able to turn off the function of specific genes, attached them to highly concentrated viruses, and then, using ultrasound to guide the needle without damaging surrounding tissue, they injected the viruses into the sacs of mouse embryos.”The virus is absorbed and integrated into the chromosomes of the single layer of surface cells that cover the tiny embryo,” explains Fuchs. “As the embryo develops, this layer of cells becomes the skin, mammary glands and oral tissue, enabling us to efficiently, selectively and quickly eliminate the expression of any desired gene in these tissues. The non-invasive method avoids triggering a wound or inflammatory response that is typically associated with conventional methods to knockdown a gene in cultured cells and then engraft the cells onto a mouse.”When the mice grew, the researchers determined which genes, when turned off, were promoting tumor growth, and what they found was surprising.”Among the seven novel tumor suppressor genes we found, our strongest hit was Myh9, which codes for the protein myosin IIa, a motor protein with well-known function in cell structure and cell migration,” says Schramek. …

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RNA sequencing of 750-year-old barley virus sheds new light on the Crusades

Scientists have for the first time sequenced an ancient RNA genome — of a barley virus once believed to be only 150 years old — pushing its origin back at least 2,000 years and revealing how intense farming at the time of the Crusades contributed to its spread.Researchers at the University of Warwick have detected and sequenced the RNA genome of Barley Stripe Mosaic Virus (BSMV) in a 750-year-old barley grain found at a site near the River Nile in modern-day Egypt. Their study is published in the journal Scientific Reports.This new find challenges current beliefs about the age of the BSMV virus, which was first discovered in 1950 with the earliest record of symptoms just 100 years ago.Although ancient DNA genomes have been sequenced before, ancient RNA genomes have not been as RNA breaks down more rapidly than DNA — generally around 50 times as fast.However in extremely dry conditions, such as those at the site in Qasr Ibrim in Lower Nubia where the barley was found, RNA can be better preserved and this has allowed the scientists to successfully sequence its genome.Using the new medieval RNA to calibrate estimates of the rate of mutations, the researchers were able to trace the evolution of the Barley Stripe Mosaic Virus to a probable origin of around 2,000 years ago, but potentially much further back to the domestication of barley in the Near East around 11,000 years ago.BSMV is transmitted through seed-to-seed contact so it is likely to originally have been transferred from the wild grass population to an early cultivated form of barley while the seeds were stored.Dr Robin Allaby of the School of Life Sciences at the University of Warwick, who led the study, said: “It is important to know as much as we can about virus evolution as emerging infectious plant diseases are a growing threat to global food security, and of those viruses account for almost half.”History tells us about the devastation caused by the emergence of disease from wild hosts in disparate countries, such as the Central American origin of the oomycete that led to the Irish potato famine.”We need to build up an accurate picture of the evolution of different types of virus so we can make better decisions about policies on plant movement.”The medieval RNA from Qasr Ibrim gives us a vital clue to unlock the real age of the Barley Stripe Mosaic Virus.”It is very difficult to understand how a plant disease evolved by solely relying on recent samples, however this 750-year-old example of the virus allows us to more accurately estimate its evolution rates and date of origin.”Without the Medieval RNA evidence, the virus appears to be much younger than it actually is, when in fact its origins go back thousands of years.”It’s possible that other viruses that similarly appear to be very recent may in fact have a more ancient origin.”The researchers believe that the Medieval BSMV genome came from a time of rapid expansion of the plant disease in the Near East and Europe.This coincided with the tumult of the Crusades which saw the Christian lands of Europe take arms against the Muslim territories of the Near East with their sights set on the city of Jerusalem. The seventh Crusade of Louis IX in 1234 is the most closely aligned in date to the origin of the virus expansion.The researchers believe the massive war effort could have caused the virus to spread, fuelled by an intensification of farming in order to feed the armies engaged in the campaign.This made contact with cultivated barley and wild grass more likely, providing opportunities for the virus to ‘jump’ into the crop.Genetic evidence also points to a split into an east and west BSMV lineage around the end of the 15th century, around 100 years after the Mongol Empire stabilised the Silk Road. It is likely that BSMV was transported to the east via trade routes such as the Silk Road in the late Medieval period.In more recent history, the virus appears to have spread to the US from Europe around 120-150 years ago.The research was supported by the research funding body BBSRC.Story Source:The above story is based on materials provided by University of Warwick. Note: Materials may be edited for content and length.

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Trick identified that aids viral infection

Scientists have identified a way some viruses protect themselves from the immune system’s efforts to stop infections, a finding that may make new approaches to treating viral infections possible.Viruses have well-known strategies for slipping past the immune system. These include faking or stealing a molecular identification badge that prevents a cell from recognizing a virus.Scientists at Washington University School of Medicine in St. Louis and elsewhere have found some viruses have another trick. They can block the immune system protein that checks for the identification badge.The blocking structure is called a stem-loop, found at the beginning of the virus’s genetic material. This is the first time scientists have found an immune-fighting mechanism built directly into the genetic material of a virus. They are looking for ways to disable it and searching for similar mechanisms that may be built into the genetic material of other disease-causing microorganisms.”When the stem-loop is in place and stable, it blocks a host cell immune protein that otherwise would bind to the virus and stop the infectious process,” said senior author Michael Diamond, MD, PhD, professor of medicine. “We found that changing a single letter of the virus’s genetic code can disable the stem-loop’s protective effects and allow the virus to be recognized by the host immune protein. We hope to find ways to weaken the stem-loop structure with drugs or other treatments, restoring the natural virus-fighting capabilities of the cell and stopping or slowing some viral infections.”Most life forms encode their genes in DNA. To use the instructions contained in DNA, though, cells have to translate them into a related genetic material, RNA, that can be read by a cell’s protein-making machinery.Some viruses encode their genes directly in RNA. Examples include West Nile virus and influenza virus, and the viruses that cause sudden acute respiratory syndrome (SARS), yellow fever and polio.When a virus infects a cell, it co-opts the cell’s protein-making machinery to make viral proteins. …

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Detailed look at HIV in action: Researchers gain a better understanding of the virus through electron microscopy

The human intestinal tract, or gut, is best known for its role in digestion. But this collection of organs also plays a prominent role in the immune system. In fact, it is one of the first parts of the body that is attacked in the early stages of an HIV infection. Knowing how the virus infects cells and accumulates in this area is critical to developing new therapies for the over 33 million people worldwide living with HIV. Researchers at the California Institute of Technology (Caltech) are the first to have utilized high-resolution electron microscopy to look at HIV infection within the actual tissue of an infected organism, providing perhaps the most detailed characterization yet of HIV infection in the gut.The team’s findings are described in the January 30 issue of PLOS Pathogens.”Looking at a real infection within real tissue is a big advance,” says Mark Ladinsky, an electron microscope scientist at Caltech and lead author of the paper. “With something like HIV, it’s usually very difficult and dangerous to do because the virus is an infectious agent. We used an animal model implanted with human tissue so we can study the actual virus under, essentially, its normal circumstances.”Ladinsky worked with Pamela Bjorkman, Max Delbrck Professor of Biology at Caltech, to take three-dimensional images of normal cells along with HIV-infected tissues from the gut of a mouse model engineered to have a human immune system. The team used a technique called electron tomography, in which a tissue sample is embedded in plastic and placed under a high-powered microscope. Then the sample is tilted incrementally through a course of 120 degrees, and pictures are taken of it at one-degree intervals. All of the images are then very carefully aligned with one another and, through a process called back projection, turned into a 3-D reconstruction that allows different places within the volume to be viewed one pixel at a time.”Most prior electron microscopy studies of HIV have focused on the virus itself or on infection of laboratory-grown cell cultures,” says Bjorkman, who is also an investigator with the Howard Hughes Medical Institute. …

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Foot and mouth disease in sub-Saharan Africa moves over short distances; wild buffalo a problem

Oct. 22, 2013 — New research shows that in sub-Saharan Africa the virus responsible for foot and mouth disease (FMD) moves over relatively short distances and the African buffalo are important natural reservoirs for the infection. The study, published in mBio®, the online open-access journal of the American Society for Microbiology, sheds light on how the type of FMD virus called SAT 2 emerged in sub-Saharan Africa and identifies patterns of spread in countries where SAT 2 is endemic.”The data suggest that the common ancestor of all SAT 2 was in [African] buffalo. It’s very clear that historically infections have moved from buffalo to cattle,” says corresponding author Matthew Hall of the University of Edinburgh in Scotland.Foot and mouth disease (FMD) is devastating to livestock all over the world, but it’s a particular problem in Africa, where wildlife that harbor the virus are thought to pass it on to their domesticated cousins.FMD strikes cloven-hoofed animals, presenting as a high fever, blistering in the mouth and feet, decline in milk production in females, and weight loss. Although most animals recover over the course of months, some die of complications from the disease. In wild buffalo, the disease is very rarely symptomatic and animals can be persistently infected for a period of several years. The SAT 2 serotype of the virus is endemic in sub-Saharan Africa, but it has crossed the Sahara and caused outbreaks in North Africa and the Middle East between 1990 and 2012.In the hopes they could eventually predict future outbreaks, Hall and his colleagues wanted a better picture of the diversity of SAT 2 viruses in sub-Saharan Africa and how they move around from one location to another. They used 250 genetic sequences of the VP1 section of the genome from SAT 2 isolates taken from all over sub-Saharan Africa and tracked the appearance of the various unique ‘topotypes’ over the region.Hall says the patterns in which the topotypes appear in different places gives strong support to the idea that the virus is spread by infected hosts in land movements over relatively short distances. What’s more, African buffalo are an important “maintenance host,” meaning they maintain a reservoir of the virus that can re-infect domesticated animals after time and culling has ended an outbreak among livestock. The relationships between the 250 sequences also indicate that it’s possible the original source of the SAT 2 viruses that are now found in wild and domesticated animals was African buffalo.To Hall, these results indicate that genetic tracking of viruses has a lot of potential for making inferences about viral spread and heading off future outbreaks.”We showed that we can demonstrate [virus movement] using genetic data. …

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Researchers advance toward engineering ‘wildly new genome’

Oct. 17, 2013 — In two parallel projects, researchers have created new genomes inside the bacterium E. coli in ways that test the limits of genetic reprogramming and open new possibilities for increasing flexibility, productivity and safety in biotechnology.In one project, researchers created a novel genome — the first-ever entirely genomically recoded organism — by replacing all 321 instances of a specific “genetic three-letter word,” called a codon, throughout the organism’s entire genome with a word of supposedly identical meaning. The researchers then reintroduced a reprogramed version of the original word (with a new meaning, a new amino acid) into the bacteria, expanding the bacterium’s vocabulary and allowing it to produce proteins that do not normally occur in nature.In the second project, the researchers removed every occurrence of 13 different codons across 42 separate E. coli genes, using a different organism for each gene, and replaced them with other codons of the same function. When they were done, 24 percent of the DNA across the 42 targeted genes had been changed, yet the proteins the genes produced remained identical to those produced by the original genes.”The first project is saying that we can take one codon, completely remove it from the genome, then successfully reassign its function,” said Marc Lajoie, a Harvard Medical School graduate student in the lab of George Church. “For the second project we asked, ‘OK, we’ve changed this one codon, how many others can we change?'”Of the 13 codons chosen for the project, all could be changed.”That leaves open the possibility that we could potentially replace any or all of those 13 codons throughout the entire genome,” Lajoie said.The results of these two projects appear today in Science. The work was led by Church, Robert Winthrop Professor of Genetics at Harvard Medical School and founding core faculty member at the Wyss Institute for Biologically Inspired Engineering. Farren Isaacs, assistant professor of molecular, cellular, and developmental biology at Yale School of Medicine, is co-senior author on the first study.Toward safer, more productive, more versatile biotechRecoded genomes can confer protection against viruses — which limit productivity in the biotech industry — and help prevent the spread of potentially dangerous genetically engineered traits to wild organisms.”In science we talk a lot about the ‘what’ and the ‘how’ of things, but in this case, the ‘why’ is very important,” Church said, explaining how this project is part of an ongoing effort to improve the safety, productivity and flexibility of biotechnology.”These results might also open a whole new chemical toolbox for biotech production,” said Isaacs. “For example, adding durable polymers to a therapeutic molecule could allow it to function longer in the human bloodstream.”But to have such an impact, the researchers said, large swaths of the genome need to be changed all at once.”If we make a few changes that make the microbe a little more resistant to a virus, the virus is going to compensate. …

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How a ubiquitous herpesvirus sometimes leads to cancer

Oct. 10, 2013 — You might not know it, but most of us are infected with the herpesvirus known as Epstein-Barr virus (EBV). For most of us, the virus will lead at worst to a case of infectious mononucleosis, but sometimes, and especially in some parts of the world, those viruses are found in association with cancer. Now, researchers reporting in the Cell Press journal Cell Reports on October 10 have found that the difference between a relatively harmless infection and a cancer-causing one lies at least partly in the viral strain itself.Share This:The results offer some of the first evidence for the existence of distinct EBV subtypes with very different public health risks. The researchers say that vaccination or other strategies for preventing EBV infection will need to be designed with these most pathogenic, cancer-causing strains in mind.”EBV is an important but neglected pathogen,” said Henri-Jacques Delecluse of the German Cancer Research Centre in Heidelberg, Germany. “We have made an important step in recognizing that EBV is actually a family of viruses that have different properties, some of which are very likely to cause disease. So, the consequences of being infected with EBV might be different, depending on the strain one carries.”Delecluse and his colleagues made the discovery by sequencing the DNA of a viral strain dubbed M81 isolated from a Chinese patient with nasopharyngeal carcinoma (NPC). Their analyses revealed that M81 is highly similar to other viruses isolated from NPCs and profoundly different from Western strains in terms of its ability to infect and replicate within cells.The M81 strain can infect epithelial cells and multiply spontaneously at a very high level in all cells it infects, including B lymphocytes, the cells in which the viruses hide, the researchers report. It remains to be seen exactly how infected epithelial cells become cancerous.”Our results have made me radically change my strategy to address the problem of EBV-associated diseases,” Delecluse said. “The current view is that the virus is essentially the same all over the world and that local conditions explain the different consequences of EBV infection. …

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Effects of climate change on West Nile virus

Sep. 9, 2013 — The varied influence of climate change on temperature and precipitation may have an equally wide-ranging effect on the spread of West Nile virus, suggesting that public health efforts to control the virus will need to take a local rather than global perspective, according to a study published this week in the scientific journal Proceedings of the National Academy of Sciences.University of Arizona researchers Cory Morin and Andrew Comrie developed a climate-driven mosquito population model to simulate the abundance across the southern United States of one type of mosquito known to carry and spread West Nile virus to humans. They found that, under the future climate conditions predicted by climate change models, many locations will see a lengthening of the mosquito season but shrinking summer mosquito populations due to hotter and dryer conditions allowing fewer larvae to survive.However, these changes vary significantly depending on temperature and precipitation. For example, drops in summer mosquito populations are expected to be significant in the South, but not further north where there will still be enough rain to maintain summer breeding habitats and extreme temperatures are less common. These findings suggest that disease transmission studies and programs designed to control populations of disease-carrying mosquitoes must be targeted locally to maximize their effectiveness, the authors argue.”It used to be an open question whether climate change is going to make disease-carrying mosquitoes more abundant, and the answer is it will depend on the time and the location,” said Morin, who did the study as part of his doctoral dissertation in the lab of Comrie, UA provost and professor in the UA’s School of Geography and Development. Morin is now a postdoctoral researcher on Comrie’s team.”One assumption was that with rising temperatures, mosquitoes would thrive across the board,” Morin said. “Our study shows this is unlikely. Rather, the effects of climate change are different depending on the region and because of that, the response of West Nile virus transmitting mosquito populations will be different as well.””The mosquito species we study is subtropical, and at warmer temperatures the larvae develop faster,” Morin explained. “However, there is a limit — if temperatures climb over that limit, mortality increases. Temperature, precipitation or both can limit the populations, depending on local conditions.”In the southwestern U.S. …

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Pain-free microneedle influenza vaccine is effective, long-lasting

Sep. 4, 2013 — Scientists have developed an influenza vaccine delivered via microneedle patch that provided 100 percent protection against a lethal influenza virus in mice more than one year after vaccination. They report their findings in the September 2013 issue of the journal Clinical and Vaccine Immunology.Share This:Microneedles are a medium for delivery of influenza vaccine that avoids the pain associated with ordinary hypodermic needles. They are a mere seven tenths of a millimeter in length, and the volume of vaccine — a major contributor to pain — is minuscule.Instead of a liquid containing whole killed or attenuated virus, this vaccine uses dry virus-like particles (VLPs) which simply coat the needles in the presence of a simple stabilizing agent, reducing the need for refrigeration — a potential boon for use in developing countries. The lower dose required when using microneedles also reduces the potential for side effects, such as lung inflammation.”This method can induce higher levels of IgG2a antibodies as well as rapid recall immune responses following lethal challenge infection. Our previous study showed that microneedle vaccination induced higher levels of antibody-secreting cells in spleen and bone marrow compared to intramuscular vaccination,” says Sang-Moo Kang of Georgia State University, a researcher on the study.Earlier studies by this group showed that influenza VLP-coated microneedles actually produced higher short-term protection than conventional intramuscular immunization. In this study the researchers tested how effective the long-term protection of the vaccine was. Mice that received the vaccine were 100 percent protected from a lethal challenge with the influenza virus 14 months after vaccination.Kang says his aim was to develop an easier and pain-free method of vaccine delivery. He also says that patients could probably use this system to vaccinate themselves.Share this story on Facebook, Twitter, and Google:Other social bookmarking and sharing tools:|Story Source: The above story is based on materials provided by American Society for Microbiology. Note: Materials may be edited for content and length. …

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A virus changes its stripes: Human outbreak of eastern equine encephalitis

Aug. 22, 2013 — In the summer of 2010, the eastern Panamanian province of Darien experienced a phenomenon that had never been seen before in Latin America: a human outbreak of eastern equine encephalitis.The mosquito-borne virus that causes the disease is found all over the Americas, and infects horses throughout its range. Human infections are diagnosed every year in North America and are taken quite seriously; they carry a 50 percent chance of mortality, and can result in lifelong neurological damage. But 2010 marked a dramatic change in the way the virus behaved in Latin America.”Until the Darien outbreak, we had become convinced that the virus in South America was fundamentally different in its ability to infect people and cause serious disease,” said University of Texas Medical Branch at Galveston professor Scott Weaver, senior author of a paper on the epidemic appearing in the August 22 issue of the New England Journal of Medicine. “This epidemic broke that dogma’s back very quickly.”UTMB researchers collaborated with Panamanian scientists to investigate the outbreak, testing samples from 174 patients and many horses. In the end, they confirmed 13 human cases of eastern equine encephalitis and one case of dual infection of both eastern and Venezuelan equine encephalitis.”We saw only about a one in 10 case-fatality rate in Panama, which is low by U.S. standards,” Weaver said. “Still, if this virus has changed and become more virulent for people, we need to know, number one, is it going to spread to other parts of Latin America or number two, are other Latin American strains likely to do the same thing?”Weaver noted that earlier studies have shown that the eastern equine encephalitis virus is common in many Latin American locations where human exposure to virus-carrying mosquitoes is high. Since the virus is constantly mutating, it’s possible that a strain like the one seen in 2010 in Panama could take hold in an ecosystem in nearby Colombia, Ecuador or the Peruvian Amazon.”With a situation where a lot of people are being exposed to the virus, there would be the potential for a lot of new disease,” Weaver said. “So it’s important to understand what’s happening in Panama both for the Panamanians and for people all over Latin America.”

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First pre-clinical gene therapy study to reverse Rett symptoms

Aug. 20, 2013 — The concept behind gene therapy is simple: deliver a healthy gene to compensate for one that is mutated. New research published today in the Journal of Neuroscience suggests this approach may eventually be a feasible option to treat Rett Syndrome, the most disabling of the autism spectrum disorders. Gail Mandel, Ph.D., a Howard Hughes Investigator at Oregon Health and Sciences University, led the study. The Rett Syndrome Research Trust, with generous support from the Rett Syndrome Research Trust UK and Rett Syndrome Research & Treatment Foundation, funded this work through the MECP2 Consortium.In 2007, co-author Adrian Bird, Ph.D., at the University of Edinburgh astonished the scientific community with proof-of-concept that Rett is curable, by reversing symptoms in adult mice. His unexpected results catalyzed labs around the world to pursue a multitude of strategies to extend the pre-clinical findings to people.Today’s study is the first to show reversal of symptoms in fully symptomatic mice using techniques of gene therapy that have potential for clinical application.Rett Syndrome is an X-linked neurological disorder primarily affecting girls; in the US, about 1 in 10,000 children a year are born with Rett. In most cases symptoms begin to manifest between 6 and 18 months of age, as developmental milestones are missed or lost. The regression that follows is characterized by loss of speech, mobility, and functional hand use, which is often replaced by Rett’s signature gesture: hand-wringing, sometimes so intense that it is a constant during every waking hour. Other symptoms include seizures, tremors, orthopedic and digestive problems, disordered breathing and other autonomic impairments, sensory issues and anxiety. Most children live into adulthood and require round-the-clock care.The cause of Rett Syndrome’s terrible constellation of symptoms lies in mutations of an X-linked gene called MECP2 (methyl CpG-binding protein). …

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New strategy to disarm the dengue virus brings new hope for a universal dengue vaccine

Aug. 13, 2013 — A new strategy that cripples the ability of the dengue virus to escape the host immune system has been discovered by A*STAR’s Singapore Immunology Network (SIgN). This breakthrough strategy opens a door of hope to what may become the world’s first universal dengue vaccine candidate that can give full protection from all four serotypes of the dreadful virus.This research done in collaboration with Singapore’s Novartis Institute of Tropical Diseases (NITD) and Beijing Institute of Microbiology and Epidemiology is published in the Plos Pathogens journal, and is also supported by Singapore STOP Dengue Translational and Clinical Research (TCR) Programme grant.Early studies have shown that a sufficiently weakened virus that is still strong enough to generate protective immune response offers the best hope for an effective vaccine. However, over the years of vaccine development, scientists have learnt that the path to finding a virus of appropriate strength is fraught with challenges. This hurdle is compounded by the complexity of the dengue virus. Even though there are only four different serotypes, the fairly high rates of mutation means the virus evolve constantly, and this contributes to the great diversity of the dengue viruses circulating globally. Furthermore, in some cases, the immune response developed following infection by one of the four dengue viruses appears to increase the risk of severe dengue when the same individual is infected with any of the remaining three viruses. With nearly half the world’s population at risk of dengue infection and an estimated 400 million people getting infected each year[2], the need for a safe and long-lasting vaccine has never been greater.The new strategy uncovered in this study overcomes the prevailing challenges of vaccine development by tackling the virus’ ability to ‘hide’ from the host immune system. Dengue virus requires the enzyme called MTase (also known as 2′-O-methyltransferase) to chemically modify its genetic material to escape detection. In this study, the researchers discovered that by introducing a genetic mutation to deactivate the MTase enzyme of the virus, initial cells infected by the weakened MTase mutant virus is immediately recognised as foreign. …

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First probable person to person transmission of new bird flu virus in China; But H7N9 is not able to spread efficiently between humans

Aug. 6, 2013 — The first report of probable person to person transmission of the new avian influenza A (H7N9) virus in Eastern China has just been published.The findings provide the strongest evidence yet of H7N9 transmission between humans, but the authors stress that its ability to transmit itself is “limited and non-sustainable.”Avian influenza A (H7N9) virus was recently identified in Eastern China. As of 30 June 2013, 133 cases have been reported, resulting in 43 deaths.Most cases appear to have visited live poultry markets or had close contact with live poultry 7-10 days before illness onset. Currently no definite evidence indicates sustained human-to-human transmission of the H7N9 virus.The study reports a family cluster of two patients (father and daughter) with H7N9 virus infection in Eastern China in March 2013.The first (index) patient — a 60 year old man — regularly visited a live poultry market and became ill five to six days after his last exposure to poultry. He was admitted to hospital on 11 March.When his symptoms became worse, he was transferred to the hospital’s intensive care unit (ICU) on 15 March. He was transferred to another ICU on March 18 and died of multi-organ failure on 4 May.The second patient, his healthy 32 year old daughter, had no known exposure to live poultry before becoming sick. However, she provided direct and unprotected bedside care for her father in the hospital before his admission to intensive care.She developed symptoms six days after her last contact with her father and was admitted to hospital on 24 March. She was transferred to the ICU on 28 March and died of multi-organ failure on 24 April.Two almost genetically identical virus strains were isolated from each patient, suggesting transmission from father to daughter.Forty-three close contacts of both cases were interviewed by public health officials and tested for influenza virus. Of these, one (a son in law who helped care for the father) had mild illness, but all contacts tested negative for H7N9 infection.Environmental samples from poultry cages, water at two local poultry markets, and swans from the residential area, were also tested. One strain was isolated but was genetically different to the two strains isolated from the patients.The researchers acknowledge some study limitations, but say that the most likely explanation for this family cluster of two cases with H7N9 infection is that the virus “transmitted directly from the index patient to his daughter.” But they stress that “the virus has not gained the ability to transmit itself sustained from person to person efficiently.”They believe that the most likely source of infection for the index case was the live poultry market, and conclude: “To our best knowledge, this is the first report of probable transmissibility of the novel virus person to person with detailed epidemiological, clinical, and virological data. …

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Learning from a virus: Keeping genes under wraps

July 30, 2013 — An international collaboration of researchers including Felicia Goodrum of the University of Arizona’s immunobiology department has studied how a human herpes virus carried by the majority of the population packages its genetic information during infection.The discoveries improve the chances of developing more targeted therapies in place of existing drugs, which do not always work or come with side effects.Experts estimate that 60 to 90 percent of the world’s population carry the human cytomegalovirus, or CMV, which is one of the eight herpes viruses that infect humans.In healthy individuals, the virus lies dormant and does not cause overt disease. However, it poses a significant risk when contracted by unborn children — whose immune system has not matured yet — and individuals with compromised immune function.CMV is the leading cause of birth defects resulting from any infectious agent. It affects one in 150 births in the US and most commonly results in hearing loss, but can also cause cognitive or physical anomalies and cerebral palsy. Once infected, the virus stays in the body for life and flares up only when the immune system is suppressed, for example in AIDS patients, transplant patients and cancer patients undergoing intensive chemotherapy.For the study, published in the scientific journal Proceedings of the National Academy of Sciences (PNAS), Goodrum teamed up with collaborators in Germany and Israel.The researchers investigated how a fundamental aspect of the human cell regulates the virus: the mechanism by which genetic information is packaged and stored. Understanding how the viral DNA behaves in the human host cells during dormancy and reactivation of the virus provides the basis for the development of drugs that could prevent the virus from “waking up” and causing disease.”The human immune system is very sophisticated, and the way this virus has managed to stealthily integrate into our biology to ensure its own survival is no small feat,” said Goodrum, also a member of the UA’s BIO5 Institute.”CMV is a master of human cell biology. From transcribing DNA into blueprints for proteins to the manufacturing of those proteins, from cell division to cellular metabolism, there is not a process this virus has not tweaked,” Goodrum also said.That mastery, she explained, is the reason the virus is so elusive to vaccine, and there currently is no way to eradicate it. Goodrum noted that with other herpes viruses, like Epstein-Barr or chicken pox, the infection is obvious. But that is not the case with CMV.”From the perspective of a virus, that is the pinnacle of mastery — to infect without ever making its presence known,” Goodrum said.”To develop more effective antiviral strategies, we must understand the biology of the virus infection and how the virus manages to persist for our lifetimes,” she said. “We are trying to understand how our cellular mechanisms are being used by this virus and discover targets for drugs to control it.”Each human cell contains a thread of DNA that is about 6 feet long, stowed away in its nucleus and tightly packaged by proteins called histones. One such package of genetic material is called a chromosome.”You can imagine histones as a spool, and the thread is DNA that wraps around the spool,” Goodrum said. …

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Monoclonal antibody effective against norovirus

July 24, 2013 — Researchers from the National Institute of Allergy and Infectious Diseases (NIAID) provide the first proof of concept data showing that a monoclonal antibody can neutralize human norovirus. This research, which could one day lead to effective therapies against the virus, was published online ahead of print in the Journal of Virology.Share This:”We initiated this work because there is presently no virus-specific treatment or vaccine to control the norovirus illness,” says Kim Y. Green, a researcher on the study. “Our working hypothesis was that a highly specific norovirus antibody that binds to the outer surface of the virus particle might prevent the ability of the virus to infect susceptible host cells.”The team first isolated genes from chimpanzee immune cells encoding norovirus-specific antibodies. They then converted these into human-compatible full-length immunoglobulin molecules. They successfully tested two of the antibodies against norovirus infection in chimpanzees.”An effective therapeutic antibody might be explored as both a treatment for norovirus gastroenteritis, and as a disease prevention strategy,” says Green. “Consider a developing outbreak scenario in which food-handlers, healthcare workers, deployed military, or travelers could reduce risk of infection, incapacitation, and spread if a safe and inexpensive treatment is immediately available.”Norovirus causes roughly 20 million cases of acute diarrhea and vomiting annually in the US, alone, according to the US Centers for Disease Control and Prevention (CDC). While in most people, symptoms last a day or two, for those with impaired immune systems, and the young and the aged, norovirus can be life-threatening. It is responsible for an estimated 70,000 hospitalizations and 800 deaths annually, and roughly one in 15 Americans get the disease every year. It is unusually contagious, via the fecal-oral route. …

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Does the dangerous new Middle East coronavirus have an African origin?

July 24, 2013 — The MERS-coronavirus is regarded as a dangerous novel pathogen: Almost 50 people have died from infection with the virus since it was first discovered in 2012. To date all cases are connected with the Arabian peninsula. Scientists from the University Bonn (Germany) and South Africa have now detected a virus in the faeces of a South African bat that is genetically more closely related to MERS-CoV than any other known virus. The scientists therefore believe that African bats may play a role in the evolution of MERS-CoV predecessor viruses.Their results have just been published online in the journal Emerging Infectious Diseases.Infection with the novel “Middle East Respiratory Syndrome Coronavirus” or MERS-CoV has been diagnosed in 90 patients so far, half of whom have died. In severe cases, patients develop pneumonia and acute kidney failure. All cases so far are – sometimes indirectly through infected family members or close contacts – connected with the Arabian peninsula.A collaboration of researchers from the Institute of Virology at the University Bonn, Germany, the University of Stellenbosch and several other South African institutions have recently found evidence that MERS-CoV could possibly originate from bats occurring in southern Africa. The South African scientists, headed by Prof. Wolfgang Preiser, tested faecal material from a total of 62 bats from 13 different species for coronaviruses. In collaboration with their colleagues in Bonn, headed by Dr. Jan Felix Drexler, they investigated the genetic material of the viruses that they found.In a faecal sample from a bat of the species Neoromicia cf. …

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Vulnerabilities of the deadly Ebola virus identified

July 23, 2013 — Disabling a protein in Ebola virus cells can stop the virus from replicating and infecting the host, according to researchers from the Icahn School of Medicine at Mount Sinai. The data are published in July in the journal Cell Host and Microbe.Ebola viruses cause severe disease in humans because they can deactivate the innate immune system. Christopher Basler, PhD, Associate Professor of Microbiology at Mount Sinai and his team have studied how Ebola viruses evade the immune system, and discovered that a viral protein called VP35 is critical to deactivating the immune system. They found that when VP35 interacts with an important cellular protein called PACT, it blocks PACT from activating the immune system, allowing the virus to spread.”Ebola viruses are extremely lethal, and are a great threat to human health as a bioweapon,” said Dr. Basler. “Currently, there is no approved vaccine or treatment. Our findings will hopefully pave the way for future antiviral treatments.”With the help of collaborators at the University of Texas with access to special high containment facilities, Dr. Basler and his team infected healthy cells with Ebola virus cells that had mutated versions of VP35. The mutations disabled VP35’s ability to interact with PACT, therefore allowing it to activate the immune system and prevent the virus from replicating. Next, the researchers overexpressed PACT in healthy cells, and infected them with Ebola virus cells. …

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Study lays groundwork for norovirus anti-viral treatments

July 22, 2013 — An animal model of the human norovirus created at the University of Michigan Health System lays the groundwork for understanding the biology of the pesky virus and developing antiviral drug treatment.Well-known as the virus that impacts cruise ship vacations, norovirus leads to misery on land too. The virus spreads quickly from person to person in any closed-in space, such as schools, nursing homes, or day-care centers.”The first virus in this group was discovered in 1972 following a disease outbreak at a school in Norwalk, Ohio in 1968. Since then research has been underway to culture noroviruses in the laboratory and develop animal models,” says lead researcher Christiane Wobus, Ph.D., assistant professor in the Department of Microbiology and Immunology at the University of Michigan Medical School.An international group of scientists from the U.S. and Germany authored the study published in mBIO, a journal of the American Society of Microbiology.”Norovirus research has been hampered by the absence of a norovirus cell culture and a genetically manipulable small animal model,” Wobus says. “This new model gives us the tool to test potential antiviral compounds and may lay the foundation to culture these viruses in the lab.”The new model was developed by determining whether human noroviruses can infect “humanized” mice, that is mice containing human immune cells. These mice are widely used for study of the human immunodeficiency virus (HIV), a virus which can only infect human cells.The study identified macrophages, a vital immune cell in the body, as the cell type infected by the virus.Very few particles of the virus can lead to infection. Estimates are as few as 18 particles can cause gastroenteritis (inflammation of the stomach and intestines) and lead to diarrhea, vomiting and stomach pain. In the U.S. norovirus causes approximately 21 million cases of acute gastroenteritis a year, and 800 deaths.”Most people can cope with the symptoms, but deaths are more likely among the elderly mainly because of dehydration,” Wobus says.Only the common cold is more widespread than the norovirus, which can remain on surfaces for weeks, ready to cause more infections. Because it lacks a lipid envelope, norovirus is not susceptible to common disinfectants and alcohol-based sanitizers.The economic impact of these infections is staggering with an economic cost for norovirus associated food-borne outbreaks alone of $5.8 billion in the U.S.There is no vaccine for preventing norovirus infection and no drug to treat it. …

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