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    Home > Active Ingredient News > Infection > HCV from discovery to conquest - a game between humans and viruses.

    HCV from discovery to conquest - a game between humans and viruses.

    • Last Update: 2020-10-19
    • Source: Internet
    • Author: User
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    The just-announced 2020 Nobel Prize in Physiology or Medicine went to Harvey J. Alter, Michael Houghton, and Charles M. Rice.
    they have made a significant contribution to the field of blood-based hepatitis research - the discovery of the hepatitis C virus.
    the discovery of the hepatitis C virus (HCV) revealed the cause of blood-based hepatitis, saving millions of lives with breakthroughs in the development of testing reagents and drug development.
    The discovery of HCV in the 1940s, two main types of infectious hepatitis: the first, called hepatitis A, was transmitted through contaminated water or food, usually with little long-term effect on patients;
    this type of hepatitis is often hidden, people after infection generally no obvious clinical symptoms, often in the later stages of the disease after the corresponding complications can be found, when people are helpless.
    to identify this potential "enemy" is the key to defeating the disease.
    In the 1960s, Baruch Blumberg discovered that a blood-based hepatitis was caused by a virus called hepatitis B virus, driving the development of diagnostic reagents and vaccines, and Bloomberg won the Nobel Prize in Physiology or Medicine in 1976.
    In the mid-1970s, Harvey J. Alter, director of the Infectious Diseases Section of the Department of Transfusion Medicine at the National Institutes of Health, and his team demonstrated that most cases of post-transfusion hepatitis were not caused by hepatitis A or hepatitis B viruses, but were unknown pathogens.
    they also found that the unknown pathogen, which is characterized by a virus, can be transmitted through the blood to chimpanzees , the only susceptible hosts outside humans.
    based on this finding, such blood transfusion-related cases were initially referred to internationally as non-A-non-hepatitis B (NANBH).
    , however, the identification of the virus has not been successful for the next decade.
    in 1987, Michael Houghton of Chiron Corporation, and two Chinese-American scientists, Qui-Lim Choo, George Kuo and Daniel Kuo of the U.S. Centers for Disease Control and Disease Control, were arrested. Daniel W. Bradley collaborated on a new molecular cloning method to identify unknown organisms and develop diagnostic tests.
    and his colleagues extracted DNA fragments from nucleic acids found in the blood of infected chimpanzees.
    most of these fragments came from chimpanzees' own genomes, but researchers predict that some of them may have come from unknown viruses.
    hypothesical that antibodies against the virus are present in the blood of hepatitis patients, the researchers used the patient's serum to identify cloned viral DNA fragments that encode viral proteins.
    after a thorough search, finally found a positive clone.
    further work showed that the clone originated from a new type of RNA virus in the yellow virus family, known as hepatitis C Virus (HCV).
    1988, Harvey Arter used the method to find the presence of antibodies in a group of NANBH specimens, strongly suggesting that the virus was a pathogen sought by scientists.
    april 1989, the discovery of the hepatitis C virus was published in the journal Science.
    2000, Art and Horton won the Rask Prize for pioneering work.
    April 1989, the discovery of the hepatitis C virus was published in the journal Science and proved decisive that HCV was the main culprit of hepatitis C.
    , the key elements of this scientific problem remain unresolved: Can the hepatitis C virus itself cause hepatitis? To answer this question, scientists had to study whether cloned viruses could replicate and cause disease.
    , however, is a seemingly unsophateable virus that has made it extremely difficult for a large number of researchers to replicate it in a laboratory environment.
    can't get experimental materials, new drug research and development is impossible to talk about.
    cloning of RNA once gave researchers hope.
    previous studies, RNA from many viruses has been found to be contagious in itself.
    RNA is transferred to the host cell, the virus's self-replication process is initiated.
    is the same with HCV? Scientists are looking forward to injecting RNA from the hepatitis C virus into cells, waiting for them to replicate themselves.
    they were disappointed by the results, a conventional method that did not work on the hepatitis C virus.
    Charles M. Rice, a researcher at Washington University in St. Louis at the time, and other teams working on the RNA virus noted the presence of a previously unknown area at the end of the hepatitis C virus genome, which they suspect may be important for virus replication.
    also observed genetic mutations in isolated virus samples and hypothesed that some of them might hinder virus replication.
    genetically engineered, Rice constructed RNA variants of the hepatitis C virus, including a new defined area of the virus genome, without inflamed genetic variants.
    the RNA was injected into the chimpanzee's liver, they detected the virus in the chimp's blood and observed pathological changes similar to those of patients with chronic liver disease.
    these findings prove that blood transfusion-mediated hepatitis can be caused solely by HCV infection.
    breakthrough was also published in the 1997 issue of science.
    Les's discovery in the journal Science in 1997 that the establishment of HCV cell line broke the bottleneck for new drug screening Although Professor Rice and his team first verified the infectiousness of the RNA virus in animal models, it was still a long way from replicating HCV in the lab.
    because of the high cost of raising orangutans and the fact that screening for hepatitis C drugs is not conducive, a cell line that allows the virus to replicate steadily is essential.
    doesn't sound difficult: just trans-dye existing "standard" RNA molecules into different existing cell line, and see which one is most efficient.
    but it's not that simple - the replication of these RNAs in cells is still inefficient.
    seems to have come to a dead end again.
    two years later, German scientist Professor Ralf Bartenschlager offered a solution.
    he made further cuts to the "common sequence" of HCV, retaining only the minimum information needed for virus replication.
    and his team expect streamlined RNA to replicate more efficiently.
    addition, they added a G418 resistance gene to the cut-out RNA sequence to quickly find cells that replicate the hepatitis C virus.
    their bold innovations have reaped amazing results.
    this approach, Professor Battenschlag found the first cell line that allows HCV to replicate efficiently, a breakthrough published in the 1999 issue of Science.
    , Professor Rice also covered in the journal Science a new cell line independently developed by his team.
    two bombshed news that has set off an entire academic community and industry -- people finally have tools that can be used to screen hepatitis C drugs.
    when Rice joined Rockefeller University in 2001, he built a system that could study the entire life cycle of the virus, discovered the subjects of HCV, and modeled humanized mice that studied HCV infection.
    can say that Rice has done a series of ground-breaking work in this field.
    the advent of new drugs, HCV was finally conquered vaccine research and development is an important means to curb infectious diseases, but because of the high variability of HCV C virus, for vaccine research and development has brought great challenges, hepatitis C vaccine has not been successfully developed.
    of the vaccine has also prompted scientists to turn more to the development of therapeutic drugs.
    as early as the mid-1980s, the application of α-interferon to treat hepatitis C has achieved some efficacy, in 1992 was officially approved by the FDA for hepatitis C treatment.
    but low cure rate, easy recurrence, drug resistance, side effects and other problems still plague hepatitis C patients.
    In 2002, a combination therapy between Pegylated interferon (PEG-IFN) and libavirin was approved, raising the cure rate to about 50 percent, but still failed to avoid the disadvantages of interferon itself.
    Michael Sofia, who has a strong chemical background, joined Farmasette Pharmaceuticals in 2005 to develop and make a breakthrough in the development of new drugs for hepatitis C drugs.
    the emergence of his new drug, Soufabwe, revolutionized the treatment of hepatitis C, the first treatment to effectively cure hepatitis C without interferon.
    , the drug has also become a major component in many treatment options, in association with HCV protease inhibitors, NS5A inhibitors, etc., to treat a wide range of hepatitis C population.
    By 2011, drug cocktail therapies containing HCV-specific direct-acting antiviral drugs (direct-acting antiviral, DAA) were used to treat HCV patients with a cure rate of about 75%;
    in medical history, only a few chronic diseases can be cured, and hepatitis C is one of them.
    Based on the changes this new hepatitis C drug brings to public health, the 2016 Rask Clinical Medicine Award honors Professor Rice and Professor Battenschlag, who founded the Department of Cultured Cells of HCV, and Dr. Sofia, who led the team in the development of Sofia.
    From the discovery of hepatitis A and non-B in humans in the 1970s until today in 2020, hepatitis C has become a curable chronic disease, with five scientists winning the Rask Prize for Medicine, known as the Nobel Prize in Windfinger, 16 years apart.
    three of the scientists, Harvey J. Alter, Michael Houghton and Charles M. Rice, won the 2020 Nobel Prize in Physiology or Medicine for their landmark achievements in hepatitis C virus research.
    what should we know about hepatitis C in the HCCP class? Q1 The main mode of transmission of HCV? Blood transmission was once the most common form of transmission of HCV.
    With the improvement of blood products testing methods, the most important mode of transmission of hepatitis C virus is through broken skin and mucous membranes, including the use of non-disposable syringes and needles, unsterilized devices, tattoos, etc.
    , sexual and mother-to-child transmission are also the modes of transmission of HCV.
    blood-free exposure generally does not infect HCV, such as kissing, hugging, sneezing/coughing, sharing cups/cutlery, etc.
    Q2 hepatitis C symptoms are more hidden, when need to go to the hospital? Most patients with hepatitis C were physically examined and found to have poor liver function, and then further examination revealed that hepatitis C was.
    usually have bad appetite, bloating, fatigue and other symptoms, to be alert to whether it is infected with hepatitis C.
    For hepatitis C, a more hidden disease, you only need to open a knife, blood transfusion, have multiple sexual partners, drug use, do a civilian, etc. , are high-risk groups, it is best to screen.
    C as long as positive, regardless of symptoms should be treated immediately, not timely treatment, may develop cirrhosis and liver cancer.
    Q3 interprets hepatitis C screening results? Two methods are usually used to detect HCV infection: one is to detect hepatitis C virus antibodies - anti-HCV, and the other is to detect the quantitative HCV-RNA.
    anti-HCV is a commonly used primary screening test, positive for being infected or having been infected with HCV, requiring further testing of HCV-RNA for explicit diagnosis.
    HCV-RNA is a confirmed test and an important indicator of treatment effectiveness evaluation.
    should I do after I have been screened for HCV by Q4? Gene testing currently has seven genotypes in humans, and patients with different genotypes have different sensitivity to drugs.
    Testing the HCV genotype before applying DAA antiviral therapy can help in the choice of treatment options and prognostic judgments, such as more options for patients with genotype 1, which has a higher recurrence rate than other genotype patients.
    the degree of cirrhosis in patients, in addition to detecting genotypes, the severity of liver disease in patients should be judged, mainly to assess the degree of liver fibrosis.
    of liver cirrhosis is important for assessing the severity and prognosis of the disease.
    best way to assess the degree of cirrhosis is to have a puncture in the liver, but some noninvasitional tests can also be performed, such as using Fibro-scan to detect the elastic hardness of the liver.
    if the patient has cirrhosis, the appropriate medication should be chosen and certain antiviral treatments should be extended appropriately.
    HBV test some patients will have a variety of hepatitis virus infection, at this time we must first identify the patient's liver disease and which virus is related.
    if the patient is an HCV, HBV combined infection, generally will.
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