The 2020 Nobel Prize in Physiology or Medicine jointly to
Harvey J. Alter, Michael Houghton and Charles M. Rice for the discovery of the hepatitis-c virus (HCV).
The discovery of HCV is a milestone in the fight against bloodborne hepatitis which was previously described as non-A, non-B hepatitis. This disease was a serious problem associated with the transfusion of blood and blood products. Because it was seen that a significant number of those receiving blood transfusions developed chronic hepatitis despite screening for blood-borne cause of hepatitis- Hepatitis B virus. So the search of an unknown infectious agent causing non-A, non-B hepatitis started.
“non-A, non-B” hepatitis
Alter and his colleagues showed that blood from these hepatitis patients could transmit the disease to chimpanzees, the only susceptible host besides humans. Later studies also demonstrated that the unknown infectious agent had the characteristics of a virus. Alter’s investigations in this way defined a new, distinct form of chronic viral hepatitis. This mysterious illness was known as “non-A, non-B” hepatitis.
Identification of Hepatitis-C virus
HCV is a RNA virus belonging to the Flavivirus family .
Houghton and his co-workers created a collection of DNA fragments from nucleic acids found in the blood of an infected chimpanzee. On the assumption that antibodies against the virus would be present in blood taken from hepatitis patients, the investigators used patient sera to identify cloned viral DNA fragments encoding viral proteins.
Could HCV alone cause hepatitis?
To answer this question the scientists had to investigate if the cloned virus was able to replicate and cause disease.
Charles M. Rice along with others working with RNA viruses noted a previously uncharacterized region at the end of the Hepatitis-C virus genome could be important for virus replication.
Rice also observed genetic variations in this region of isolated virus samples and hypothesized that some of these variations might hinder virus replication.
Through genetic engineering, Rice generated an RNA variant of the Hepatitis-C virus that included the newly defined region of the viral genome and was devoid of the inactivating genetic variations.
When this RNA was injected into the liver of chimpanzees, the virus was detected in the blood and pathological changes resembling those seen in human liver with the chronic disease were observed. This proved that Hepatitis-C virus alone could cause the unexplained cases of transfusion-mediated hepatitis.
Significance of HCV discovery
Due to their discovery, highly sensitive blood tests for the virus detection are now available and these have essentially eliminated post-transfusion hepatitis in many parts of the world. Their discovery also allowed the rapid development of antiviral drugs directed at hepatitis C. So their discovery gives a hope that the disease can now be cured and eradicated.