Discovery and research of hepatitis C virus-Thoughts from the 2020 Nobel Prize in Physiology or Medicine

Human viral hepatitis is caused by five different types of viruses. Among them, hepatitis A virus (HAV) and hepatitis E virus (HEV) are mainly transmitted through contaminated food and water, causing self-limited acute hepatitis. Hepatitis B virus (HBV), hepatitis C virus (HCV) and hepatitis D virus (HDV) are mainly transmitted through blood or body fluids, and most acute infections of these three viruses evolve into chronic infections. Without therapeutic intervention, the infected persons will carry the virus for life, leading to liver failure and cancer. HCV is a single-stranded RNA virus with a 9.6-kb genome and extremely high genetic diversity. There are currently 8 genotypes and 86 subtypes. There is no HCV vaccine yet. According to the latest World Health Organization (WHO) data, there are approximately 71.1 million hepatitis C patients worldwide. The number of people infected with HCV in China is estimated to be around 10 million, the most in the world. The 2020 Nobel Prize in Physiology or Medicine was awarded to the field of pathogen biology in recognition of Harvey J. Alter, Michael Houghton and Charles M. Rice for their remarkable contributions in discovering HCV. The discovery process of HCV is like a wonderful relay race of these three scientists. Prof. Harvey Alter and his colleagues discovered a new type of hepatitis disease (hepatitis C) in 1975, and Prof. Michael Horton and his colleagues cloned the near-full-length sequence of the viral genome that causes the new hepatitis (HCV) and revealed the biological characteristics of the pathogen in 1989; Prof. Charles Rice and his colleagues cloned the remaining sequence at the 3'-end of the HCV genome and experimentally proved that HCV RNA can cause hepatitis C if injected into animals in 1997. The discovery and cloning of HCV has greatly reduced the risk of hepatitis infection by blood transfusion and laid an important foundation for the later development of HCV cell culture models and antiviral drugs. This article intends to introduce the history of HCV discovery and to highlight the key contributions of each of the three scientists along this discovery journey. We will also introduce other major milestones in HCV research with an emphasis on the HCV cell culture model development that eventually led to the invention of highly effective antiviral drugs. Finally, we will give an update on the current status and challenges of hepatitis C prevention and control, and share some of our thoughts about future research on HCV. We hope that this essay will not only recapitulate the memorable history of HCV discovery, but also raise awareness of this terrible disease that is still imposing a threat to public health.