Nobel Prize winning discovery of hepatitis C virus: saving millions of lives

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 Nobel Prize winning discovery of hepatitis C virus: saving millions of lives


At about 17:30 on October 5, Beijing time, the 2020 Nobel Prize in physiology or medicine was announced. American virologist Harvey James alter, British biochemist Michael Houghton and American virologist Charles M. riceuff08 CharlesM.Rice uff09For his outstanding contribution in the field of hepatitis C virus, he shared this years awards.

Biography

Harvey James alter

Harvey James alter is an American virologist and transfusion medicine expert at the National Institutes of health. Born in 1935, ault received a Bachelor of Arts degree from the University of Rochester in 1956 and a medical degree in 1960. In 1964 and later Nobel laureate Baruch Samuel Blumberg discovered the Australian antigen, which was later thought to be part of the hepatitis B virus. He also used animal models to study human immunodeficiency virus and identified hepatitis C virus. He was awarded the Lasker prize for clinical medicine research in 2000 and the galdena International Award in 2013.

Michael Horton

Michael Houghton, a British biochemist, was involved in the development of hepatitis C testing. Horton was born in England in the 1950s. He received a bachelors degree from the University of East Anglia in 1972 and a doctorate in biology from Kings college, University of London, in 1977. He then worked at Searle research laboratory in Buckingham county and became head of non-A, non-B hepatitis division of Hilon in 1982. In 1986, he was involved in the discovery of the genome of hepatitis D. In 1989, he worked with qui Lim Choo, George Kuo and Daniel W. Bradleyuff08 DanielW.Bradley uff09We found hepatitis C together. In the early 1980s, Daniel Bradley isolated non-A, non-B hepatitis virus, later known as hepatitis C virus, from chimpanzee sera. Horton worked with Bradley to clone the viruses and develop a blood test method that was used in patients with liver cirrhosis and liver cancer in the early 1990s, reducing the risk of hepatitis C virus transfusion from one-third to about one in two million.

In 1992, he received the Carl randstein Memorial Award from the American blood bank association. In 1993, he won the Robert Koch prize. In 1994, he won the William Beaumont award of American Gastroenterology Association.

Charles M. rice

Charles M. riceuff08 CharlesM.Rice uff09Born in 1952, he is an American virologist. Rice graduated from the University of California at Davis in 1974 and received his doctorate in biochemistry from the California Institute of technology in 1981. Rice has been professor of Virology at Rockefeller University since 2001. In 2016, rice worked with Ralf bartenschlager and Michael J. Sophiauff08 MichaelJ.Sofia uff09He was awarded the Lasker debecki prize for clinical medicine.

Research Introduction

Three award-winning scientists made a groundbreaking discovery to identify a new virus, hepatitis C virus. Before their work, the discovery of hepatitis A and hepatitis B laid the foundation for the discovery of hepatitis C virus. However, the detection of hepatitis A and hepatitis B virus can not explain most cases of blood borne hepatitis. The discovery of hepatitis C virus revealed the cause of the remaining cases of chronic hepatitis and made blood tests and new drugs possible, saving millions of lives.

In the 1960s, Baruch Blumberg determined that a blood borne hepatitis was caused by a virus called hepatitis B virus, which led to diagnostic tests and the development of effective vaccines. For this discovery, he was awarded the 1976 Nobel Prize in physiology or medicine.

At the time, olter of the National Institutes of health studied the incidence of hepatitis in patients receiving blood transfusions. Although blood tests for hepatitis B virus have reduced the number of transfusion related hepatitis cases, ault and his colleagues have shown that a large number of hepatitis cases still exist. Around this time, they also tested for hepatitis A virus infection, and it was clear that hepatitis A was not the real cause.

Ault and his colleagues have shown that the blood of these hepatitis patients can transmit the disease to chimpanzees, the only susceptible host outside humans. Subsequent studies also showed that the unknown infectious agent had the characteristics of a virus. In this way, orters methodical research defines a new, unique type of chronic viral hepatitis. This mysterious disease is known as non-A, non-B hepatitis.

It is urgent to identify new viruses. Despite the use of all the traditional virus detection techniques, they are still unable to extract specific viruses. Horton, who works at Chiron pharmaceutical, did the hard work needed to isolate the genetic sequence of the virus. Horton and his colleagues extracted DNA fragments from nucleic acids found in infected chimpanzees blood. Most of these fragments come from chimpanzees own genomes, but researchers predict that some of them will come from unknown viruses. After a full search, they found a positive clone. Further work showed that the clone was derived from a novel RNA virus called hepatitis C virus.

The discovery of hepatitis C virus is of decisive significance. But can the virus itself cause hepatitis? To answer this question, scientists have to study whether cloned viruses can replicate and cause disease. Rice, a researcher at Washington University in St. Louis, and other RNA virus teams have discovered a previously unknown region at the end of the hepatitis C virus genome, which they suspect may be important for viral replication. Rice also observed genetic variations in the virus samples isolated, and hypothesized that some of them might hinder virus replication. Through genetic engineering, rice created a hepatitis C virus RNA variant. He injected the RNA into the chimpanzees liver and detected the virus in the blood and observed pathological changes similar to those in patients with chronic hepatitis. This also ultimately proves that hepatitis C virus may lead to unexplained cases of transfusion mediated hepatitis.

About hepatitis C virus (HCV)

HCV is a single stranded RNA virus with a diameter of less than 80 nm (36-40 nm in liver cells and 36-62 nm in blood). It is a single stranded positive strand RNA virus. The nucleocapsid is surrounded by a lipid containing envelope with spines. There are only three kinds of in vitro cell culture systems for HCV: Huh7, Huh7.5 and huh7.5.1. Chimpanzees can be infected with HCV, but the symptoms are mild.

HCV-RNA consists of about 9500-10000 BP. The 5 u2032 and 3 u2032 NCR are 319-341bp and 27-55bp respectively. There are several forward and reverse repeats in HCV-RNA, which may be related to gene replication. There is an open reading frame (ORF) downstream of the 5 u2032 noncoding region, in which the genome sequence is 5 - c-e1-e2-p7-ns2-ns3-ns4-ns5-3, It can encode a polyprotein precursor with a length of about 3014 amino acids. The latter can be cleaved into 10 kinds of viral proteins by the action of host cells and virus autoproteins, including three structural proteins, i.e. nucleocapsid protein with molecular weight of 19kd (core protein) and two glycoproteins (E1 protein with molecular weight of 33KD and E2 protein with molecular weight of 72kd) In protein, its function may be an ion channel. The nonstructural proteins include NS2, NS3, NS4A, NS5A and NS5B. The nonstructural proteins are very important to the life cycle of virus. NS2 and NS3 have protease activity and participate in the cleavage of viral polypeptide precursor. In addition, NS3 protein also has helicase activity and participates in the unwinding of HCV-RNA molecules to assist in RNA replication. The function of NS4 remains unclear. NS5A is a phosphoprotein that can interact with a variety of host cell proteins and plays an important role in virus replication. NS5B has RNA dependent RNA polymerase activity and participates in HCV genome replication.

In 1991, the food and Drug Administration (FDA) approved the first treatment for hepatitis C. The treatment includes interferon alpha-2b, but patients receiving treatment rarely achieve sustained virological response. The cure rate was only 6%. Since 1991, the efficacy of hepatitis C treatment has increased significantly, with recent therapies clearing up to 90% of patients with the virus.

In 2011, in view of the global burden of hepatitis C, which affects about 150-170 million people in the world, the World Health Organization and President Barack Obama announced that July 28 was officially recognized as World Hepatitis Day.

Now some studies have proposed the first generation of antiviral drugs protease inhibitors. Studies have shown that these drugs can directly act on the nonstructural proteins of hepatitis C virus to interrupt viral replication and assembly in host hepatocytes. When combined with pegylated interferon and ribavirin for 24-48 weeks, the cure rate of patients with hepatitis C genotype 1 increased to 70%.

Source: responsible editor of global science: Zhang Zutao_ NT5054