Three HCV discoverers won awards From 2020 Nobel Prize in physiology or medicine

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At 17:30 p.m. on October 5, Beijing time, the Nobel Prize in physiology or medicine in 2020 was announced. Harvey J. alter from the National Institutes of health, Michael Houghton from the University of Alberta in Canada and Charles M. rice of Rockefeller University in the United States were awarded the prize for the discovery of hepatitis C virus.

Source: www.nobelprize.org

This year’s Nobel Prize in physiology or medicine has been awarded to three scientists who have made great contributions to the research of blood borne hepatitis. Blood borne hepatitis is a health problem faced by the global population, which can lead to many people suffering from liver cirrhosis and even liver cancer.

Harvey J. alter from the National Institutes of health, Michael Houghton from the University of Alberta, and Charles M. from Rockefeller University Rice discovered hepatitis C virus (hereinafter referred to as “hepatitis C virus”), in previous studies, the discovery of hepatitis A virus and hepatitis B virus has continuously promoted the research in the field of blood borne hepatitis, but most blood-borne infections are still unable to be explained.

The discovery of hepatitis C virus reveals the causes of other chronic hepatitis viruses, and also makes the development of blood detection technology and new drugs possible, which may help save millions of lives in the future.

Hepatitis: a global threat to human health

Hepatitis (or hepatitis) is a compound word of liver and inflammation in Greek. Although alcoholism, environmental toxins and autoimmune diseases are the main causes of hepatitis, the main reason is still caused by virus infection.

In the 1940s, it was well recognized that there were two major infectious infections. The first was hepatitis A, which was transmitted mainly through contaminated water or food (faecal oral route). This hepatitis usually had no long-term health effects on patients.

The second type of hepatitis is transmitted through blood and body fluids, which represents a more serious health threat, usually leading to chronic hepatitis, and accompanied by liver cirrhosis or even liver cancer (Fig. 1). This form of hepatitis is very cunning and insidious, and healthy people can be infected silently for many years before serious complications occur.

The incidence rate and mortality rate of blood borne hepatitis are very high. It causes about 1 million deaths worldwide worldwide. This makes it a global health problem that is comparable to the risk of AIDS and tuberculosis.

Figure 1: there are two main forms of hepatitis: one is acute hepatitis caused by hepatitis A virus, which is mainly transmitted through contaminated water and food, and the other is caused by hepatitis B virus and hepatitis C virus (Nobel Prize in physiology or medicine this year). This blood borne hepatitis is usually a chronic disease, which will gradually progress to cirrhosis Even hepatocellular carcinoma.

Unknown infection factors

The key to successful intervention in infectious diseases is to identify the pathogen. In the 1960s, the researcher Dr. Baruch Blumberg identified a blood-borne hepatitis caused by hepatitis B virus infection. This research discovery laid a solid foundation for the development of diagnostic testing technology and effective vaccine development Blumberg won the 1976 Nobel Prize in physiology or medicine.

At that time, Harvey J. alter of the National Institutes of health was studying the incidence of hepatitis in blood transfusion patients. Although the newly discovered hepatitis B virus blood detection technology can reduce the number of transfusion related hepatitis cases, alter and his colleagues have surprisingly found that there are still a large number of hepatitis cases.

During this study, researchers developed a test for hepatitis A virus, but it is clear that hepatitis A virus does not appear to be the cause of a large number of unexplained cases.

Many people receiving blood transfusion often develop chronic hepatitis due to an unknown infectious pathogen, which may be a research topic of great concern to scientists. Later, Harvey J. alter and his colleagues found that blood from these hepatitis patients can also transmit the disease to chimpanzees, and chimpanzees are the only susceptible hosts other than humans.

The following results also showed that the unknown infectious pathogen may have the characteristics of a virus. Through his research, researcher alter defined a new and unique chronic viral infection, which was later called non-A and non-B hepatitis.

Detection of hepatitis C virus

Identifying this new virus seems to be a task that researchers must do now. After that, researchers used all the traditional technologies, but for more than a decade, researchers still couldn’t catch the mysterious virus.

At that time, Michael Houghton, who worked for Chiron, a pharmaceutical company, undertook the arduous task of isolating the viral genome sequence. Houghton and his colleagues collected a set of DNA fragments from the blood of an infected chimpanzee.

Most of these fragments come from chimpanzees’ own genomes, and researchers predict that some of them must have come from the unknown virus, and that antibodies against the mysterious virus must be present in the blood of hepatitis patients.

They then used the patient’s serum to identify cloned viral DNA fragments that encode viral proteins, and through a comprehensive search analysis, the researchers identified a positive clone. Further study found that: The Clone comes from a new type of RNA virus belonging to flavivirus family, which is named hepatitis C virus. The existence of antibodies in patients with chronic hepatitis strongly means that this virus is the missing pathogen that researchers have been looking for.

Figure 2: summary of the 2020 Nobel Prize in physiology or medicine. Harvey J. alter’s systematic studies on transfusion related hepatitis have shown that an unknown virus may be a common cause of many chronic hepatitis cases; researcher Michael Houghton used an unproven strategy to isolate a new virus called hepatitis C virus; and researcher Charles M. rice provided the final evidence that hepatitis C virus alone can induce hepatitis.

The discovery of hepatitis C virus has a decisive role and significance, but the key part of this research puzzle has been omitted. Can hepatitis C be induced only by hepatitis C virus?

To answer this question, researchers have to investigate whether a single clone of the virus can replicate and cause disease, said researcher Charles M Rice and other RNA virus scientists have discovered a previously unrecognized region at the end of the HCV genome, which they speculate is important for viral replication.

In addition, the researcher rice also observed special genetic variations in the isolated virus samples, and speculated that some of them might block the replication of the virus. Through genetic engineering, rice produced RNA mutations in hepatitis C virus, including the newly defined viral genome region, but there was no inactivated genetic variation.

When the RNA was injected into chimpanzees’ livers, the researchers detected the presence of the virus in their blood, and then observed similar pathological changes in chimpanzees as in people with chronic hepatitis, which may be the final evidence that hepatitis C virus alone induces unexplained transfusion mediated hepatitis.

The significance of winning the Nobel Prize in physiology or medicine

“The discovery of hepatitis C virus” can win the Nobel Prize in physiology or medicine, or will become a milestone for scientists to resist viral diseases in the future (see Figure 2).

Thanks to the important discoveries made by the above three scientists, it is precisely because of the discovery of hepatitis C virus that scientists have developed highly sensitive blood detection technologies. These detection technologies have basically eliminated the occurrence of post transfusion hepatitis in many parts of the world and greatly improved the health of the global population.

This discovery can also promote scientists to rapidly develop antiviral drugs against hepatitis C virus. At the same time, hepatitis C has been cured for the first time in history, which also brings certain hope for eradicating hepatitis C infected people in the world in the later stage. In order to achieve this goal, it is necessary to strengthen cooperation among countries to promote the development of blood testing and new antiviral drugs (see Figure 3).

Figure 3: the discovery of the three Nobel laureates makes the development of sensitive blood detection technology possible, which may eliminate the risk of transfusion mediated hepatitis transmission in most parts of the world, and this research breakthrough can also help researchers develop new effective therapies for hepatitis C. of course, hepatitis C is still a major health problem facing the global population, such as Now there are many opportunities to eliminate the disease.

Key research results:

【1】Alter HJ， Holland PV， Purcell RH， Lander JJ， Feinstone SM， Morrow AG， Schmidt PJ. Posttransfusion hepatitis after exclusion of commercial and hepatitis-B antigen-positive donors. Ann Intern Med. 1972；77：691-699.

【2】Feinstone SM， Kapikian AZ， Purcell RH， Alter HJ， Holland PV. Transfusion-associated hepatitis not due to viral hepatitis type A or B. N Engl J Med. 1975；292：767-770.

【3】Alter HJ， Holland PV， Morrow AG， Purcell RH， Feinstone SM， Moritsugu Y. Clinical and serological analysis of transfusion-associated hepatitis. Lancet. 1975；2：838-841.

【4】Alter HJ， Purcell RH， Holland PV， Popper H. Transmissible agent in non-A， non-B hepatitis. Lancet. 1978；1：459-463.

【5】Choo QL， Kuo G， Weiner AJ， Overby LR， Bradley DW， Houghton M. Isolation of a cDNA clone derived from a blood-borne non-A， non-B viral hepatitis genome. Science. 1989；244：359-362.

【6】Kuo G.， Choo QL， Alter HJ， Gitnick GL， Redeker AG， Purcell RH， Miyamura T， Dienstag JL， Alter CE， Stevens CE， Tegtmeier GE， Bonino F， Colombo M， Lee WS， Kuo C.， Berger K， Shuster JR， Overby LR， Bradley DW， Houghton M. An assay for circulating antibodies to a major etiologic virus of human non-A， non-B hepatitis. Science. 1989；244：362-364.

【7】Kolykhalov AA， Agapov EV， Blight KJ， Mihalik K， Feinstone SM， Rice CM. Transmission of hepatitis C by intrahepatic inoculation with transcribed RNA. Science. 1997；277：570-574.

Introduction to the winners of the 2020 Nobel Prize in physiology or medicine:

Harvey J. Alter

Born in New York in 1935, he received a bachelor’s degree in medicine from the University of Rochester School of medicine, and received medical training in the strong Memorial Hospital and the University of Seattle hospital. In 1961, he joined the National Institutes of Health (NIH) as a clinical assistant. During this period, he studied at Georgetown University for several years, and then returned to NIH again and joined the Department of transfusion medicine of clinical research center Senior research fellow.

Michael Houghton

Born in the UK, he received his doctorate from King’s College London in 1977, then joined g.d.searle & company, and worked for Chiron company in California in 1982; Michael in 2010 Houghton works at the University of Alberta in Canada. He is currently the chair of virology research at the Canadian center of excellence and professor and director of the Li Ka Shing virus Institute.

Charles M. Rice

Born in Sacramento, California in 1952, he received his doctorate from California Institute of technology in 1981 and studied for a postdoctoral degree from 1981 to 1985. In 1986, he established his own research group at the school of medicine of the University of Washington, and became an official professor in 1995. Since 2001, Charles M Rice served as a professor at Rockefeller University and served as scientific and executive director of the center for hepatitis C research at Rockefeller University from 2001 to 2018, and is still active in the research front line.

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