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Hepatitis

Description:
Hepatitis is inflammation of the liver. Several different viruses cause viral hepatitis. They are named the A, B, C, D, and E viruses. All of these viruses cause acute, or short-term, viral hepatitis. The hepatitis B, C, and D viruses can also cause chronic hepatitis, in which the infection is prolonged, sometimes lifelong. Symptoms of viral hepatitis include jaundice (yellowing of the skin and eyes), fatigue, abdominal pain, loss of appetite, nausea, vomiting, diarrhea, low grade fever, and headache.

Who is at Risk?
Risk groups depend on the type of hepatitis - A, B, C, D, or E. They include: people who have household contacts of infected persons, sex contacts of infected persons, persons traveling to countries where hepatitis is common, men who have sex with men, injecting and non-injecting drug users, persons with multiple sex partners or diagnosis of a sexually transmitted disease, infants born to infected mothers, health care and public safety workers, hemodialysis patients, recipients of clotting factors made before 1987, recipients of blood and/or solid organs before 1992, and people with undiagnosed liver problems.

Sources: National Institute of Diabetes and Digestive and Kidney Diseases, About, Inc.

TSRI Team Makes First Culture System for Hepatitis C
TSRI Professor Frank Chisari, M.D. and his colleagues have developed a way to produce the hepatitis C virus (HCV) in tissue culture. Their system will make it possible for the first time to understand all aspects of the life cycle of the virus, which in turn will lead to the development of antiviral drugs and vaccines. Until now, the inability to grow the pathogen in laboratories has delayed the development of more effective drugs and a vaccine. A liver-destroying pathogen, HCV infects 170 million people around the world and represents a growing public health burden. There are six major genetic families of HCV, and current treatments work better against some so-called genotypes than others. But a fundamental roadblock has stymied scientific progress: HCV has stubbornly refused to grow in laboratory cell cultures until now.

Chisari"s advance will finally enable researchers to study critical aspects of the pathogen"s life cycle, such as cell entry, replication, and packaging into new virus particles, each of which represents a novel drug target that has not been previously approachable. More precise targets, in turn, may yield drugs that are more effective than currently available agents, which are toxic and expensive, require a year of injections, and fail in some patients. Chisari"s other projects involve the discovery of how interferon cures hepatitis B infection by activating hepatocellular mechanisms that prevent the formation of replication competent HBV capsids and inhibit HBV replication; and how commonly used drugs that control serum cholesterol levels can also control hepatitis C virus replication by illustrating a complex cellular regulatory network that controls HCV RNA replication, presumably by modulating the trafficking and association of cellular and/or viral proteins with cellular membranes.

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Regulating Hepatitis B Gene Expression
Hepatitis B Virus (HBV) is a worldwide health problem endemic in many regions of Asia and Africa. The HBV infection can be fatal. Although it can generally be prevented by vaccination with Hepatitis B surface antigen (HBsAg), chronic HBV infection remains a major clinical problem, with an estimated 200 to 500 million HBV chronic carriers in the world, for whom, to date, there is no reliable treatment. Understanding the viral life cycle in detail may reveal potential targets for antiviral therapy to control the liver disease associated with HBV infection. TSRI Associate Professor Alan McLachlan, Ph.D. and his colleagues are currently studying the regulation of HBV gene expression and its relationship to viral replication to reveal potential targets for antiviral therapy.

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Scripps Research Institute scientists find promising vaccine targets for HCV virus
A team of scientists, led by assistant professor Mansun Law at The Scripps Research Institute, has found antibodies that can prevent infection from widely differing strains of hepatitis C virus (HCV) in cell culture and animal models. HCV’s very high rate of mutation normally helps it to evade its host’s immune system. The newly discovered antibodies, however, attach to sites on the viral envelope that seldom mutate. One of the new antibodies, AR4A, shows broader HCV neutralizing activity than any previously reported anti-HCV antibody. These antibodies attach to sites on the viral envelope that were previously unknown, but now represent promising targets for an HCV vaccine.

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Scientists Develop Process To Disrupt Hepatitis C Virion Production
Scientists at The Scripps Research Institute's Scripps Florida facilities have discovered a method to disrupt the production of infectious virus particles that cause hepatitis C, a blood-borne liver disease. This discovery might be a first step in developing new and more effective therapies against the hepatitis C virus (HCV). Current anti-virals are ineffective for many patients infected with the viral strains most prevalent in the United States. HCV is a significant human pathogen, infecting more than three percent of the world's population. The incidence of infection in the United States has been estimated to be as high as 4 million cases. Timothy Tellinghuisen, Ph.D., an assistant professor in the Department of Infectology at Scripps Florida, and his colleagues used mutations of the viral NS5A phosphoprotein to disrupt virus particle production at an early stage of assembly. NS5A has long been proposed as a regulator of events in the HCV life cycle, but exactly how it orchestrates these events has been unclear.

The interesting thing about this mutant is that while it triggers totally normal RNA replication, it causes severe defects in the output of infectious virus - in fact, it releases no infectious virus that we can detect. And though this discovery isn't a cure for HCV, it is an important research tool that stops the assembly pathway. Total disruption of the replication process would be a cure for the disease and that's the team's long-term goal.

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Scripps Research Discovery May Aid in the Development of Anti-Hepatitis C Virus Drugs
A team from The Scripps Research Institute has found a way to inhibit viral production of the Hepatitis C virus (HCV). The advance has the potential to accelerate future research on the virus life cycle and to aid in the development of novel HVC drugs. The research was led by Professor Donny Strosberg, Ph.D., of Scripps Florida, In the new study, Strosberg and his colleagues describe peptides (molecules of two or more amino acids) derived from the core protein of hepatitis C. The team found that these peptides inhibit not only dimerization of the core protein (the joining of two identical subunits), but also production of the actual virus itself. The scientists went for the simplest solution, taking a peptide from core to see if they could block the interaction, and it did.

With over 170 million people infected worldwide by HCV, new therapeutic strategies for HVC—a blood-borne disease that affects the liver—are urgently needed. But one of the critical problems in developing drugs for HCV is that it mutates at such prodigious rates. An RNA virus like hepatitis C can mutate at a rate estimated as high as one million times that of DNA viruses; in contrast, DNA viruses contain an enzyme (polymerase) that acts as something of a proof reader to ensure that newly transcribed DNA strands are the same as the original, helping to reduce mutations. In one sense, the ongoing issue with hepatitis C is that there are still so very few drugs to treat the virus and very few tools to study it. The scientists set out to develop new tools and to identify a new target – core, the capsid protein. By targeting the interactions of core with itself or other proteins, they could reduce the problem of rapid mutation not only because the core protein mutates significantly less, but also because mutations that would affect the interface between core and itself or other proteins would often be more likely to deactivate the virus, in contrast to mutations in viral enzymes which often lead to increased resistance to drugs.

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