Nobel Prize in Medicine awarded for research on hepatitis C virus

Harvey J. Alter, Michael Houghton and Charles M. Rice made fundamental discoveries that led to

identification of a new virus - hepatitis C virus. Before their work, the discoveries of hepatitis A and B viruses were also important, but most cases of blood-borne hepatitis remained unexplained. The discovery of the hepatitis C virus has identified the cause of chronic hepatitis cases and made possible new blood tests and drugs that have saved millions of lives.

Hepatitis is mainly caused by viralinfections, although alcohol abuse, environmental toxins, and autoimmune diseases also contribute to this disease. In the 1940s, it became clear that there were two main types of infectious hepatitis. The first, called hepatitis A, is transmitted through contaminated water or food and does not usually have long-term effects on the patient. The second type is transmitted through blood and body fluids and poses a much more serious threat, as it can lead to chronic disease with the development of cirrhosis and liver cancer. This form of hepatitis is insidious, as otherwise healthy people can become infected silently for years before serious complications develop. Blood-borne hepatitis is associated with significant morbidity and mortality and causes more than a million deaths per year worldwide, making it a global health problem on a scale comparable to HIV and tuberculosis.

Discovery of hepatitis A and B

The key to successful intervention againstinfectious diseases is the identification of the pathogen. In the 1960s, Baruch Bloomberg determined that a form of blood borne hepatitis was caused by a virus that became known as the hepatitis B virus. This discovery led to the development of diagnostic tests and an effective vaccine. For this discovery, Bloomberg was awarded the Nobel Prize in Physiology or Medicine in 1976.

At the time, Harvey J. Alter of the US National Institutes of Health has studied the occurrence of hepatitis in transfused patients. Although blood tests for the newly discovered hepatitis B virus reduced the incidence of transfusion-related hepatitis, Alter and his colleagues showed with dismay that a large number of infections still persisted. It was around this time that tests for hepatitis A viral infection were developed and it became clear that hepatitis A was not the cause of these unexplained cases.

It was of great concern thata significant number of those who received blood transfusions developed chronic hepatitis due to an unknown infectious agent. Alter and his colleagues showed that the blood of these hepatitis B patients can transmit disease to chimpanzees, the only susceptible host other than humans. Subsequent studies also showed that the unknown infectious agent had all the characteristics of a virus. Thus, Alter's methodological research identified a new, distinct form of chronic viral hepatitis. The mysterious disease became known as non-A, non-B hepatitis.

Detection of hepatitis C virus

Identifying a new virus has become for scientiststhe first priority. All traditional methods of searching for viruses were used, but despite this, the virus eluded isolation for more than ten years. Michael Houghton, who works for the pharmaceutical firm Chiron, did the painstaking work required to isolate the genetic sequence of the virus. Houghton and his collaborators have created a collection of DNA fragments from nucleic acids found in the blood of an infected chimpanzee. Most of these fragments came from the genome of the chimpanzee itself, but the researchers predicted that some of them would come from an unknown virus. Based on the assumption that antibodies against the virus would be present in blood taken from patients with hepatitis, the scientists used patient sera to identify cloned fragments of viral DNA encoding viral proteins. After extensive search, one positive clone was found. Further work showed that this clone descended from a new RNA virus belonging to the flavivirus family and was named the hepatitis C virus. The presence of antibodies in patients with chronic hepatitis clearly indicated to scientists that this virus was a missing agent.

The discovery of the hepatitis C virus was crucialvalue. However, researchers wondered: could the virus cause hepatitis by itself? To answer this question, scientists had to find out if the cloned virus could replicate and cause hepatitis. Charles M. Rice, a researcher at the University of Washington in St. Louis, along with scientists working with RNA viruses, noted a previously uncharacterized region at the end of the genome of the hepatitis C virus. As scientists suspected, it could be critical for the replication of the virus. Rice also observed genetic variations in isolated virus samples and suggested that some of them might interfere with viral replication. Using genetic engineering, Rice created a variant of the RNA of the hepatitis C virus that included a newly identified region of the viral genome and was devoid of inactivating genetic variation. When this RNA was injected into the chimpanzee's liver, the virus was found in the blood. Later, pathological changes were observed, similar to those observed in people with chronic hepatitis. This was the latest evidence that the hepatitis C virus itself can cause unexplained cases of transfusion-mediated hepatitis.

Opening value

Thanks to the discovery of scientists, mankind nowHighly sensitive blood tests for the virus are available and have essentially eliminated post-transfusion hepatitis in many parts of the world. Their research also led to the rapid development of antiviral drugs against hepatitis C.

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