A protracted war of human beings against virus: Interpreting for the Nobel Prize in Physiology or Medicine in 2020

Abstract

On 5th October of 2020, the Nobel committee announced in the Karolinska Institute that the 2020 Nobel Prize in Physiology or Medicine was awarded to Harvey J. Alter, Michael Houghton, and Charles M. Rice to commend their contribution in the aspect of discovering hepatitis C virus (HCV). Alter and his team acquired C100-3 protein by utilizing recombinant yeast to express viral sequence segments and found the HCV antibody by performing radioimmunoassay. Houghton and his colleagues successfully created the cDNA library from the serum of non-A and non-B hepatitis patients in bacteriophage. Subsequently, the large-scale blind screening method was performed in the serum of patients, acquired clone 81 from the library screening as the clone 5-1-1 involving short sequences to be the probe, and confirmed HCV ultimately. In 1995, Rice and his collaborators completed the full-length HCV genome sequencing from the 3′ terminal sequence using a quantitatively competitive reverse transcription PCR method and verified the full-length sequence has infectivity. This is the first causative agent entirely discovered by molecular biological techniques in human being’s history. Furthermore, Wakita with his team, acquired a full-length HCV genome from acute HCV patients and transformed viral RNA to Hun-7 cell to generate HCV virion in 2005. On this basis, Rice and his team successfully established the cell-cultured system that can effectively generate HCV with infectivity. According to the WHO latest data, there were approximately 71 million chronic HCV cases and nearly 400000 deaths globally in 2016. About 14% of the total HCV infected individuals worldwide lived in China. As a common infectious pathogen globally, HCV infection may cause severe threats and damages to human health, such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma. The high genetic variation is major characteristics of HCV, which has phylogenetically generated more than 7 genotypes and hundreds of subtypes. The various genotypes and subtypes have distinct geographic distribution and different responses on anti-virus treatment. The resistant mutation for the clinical using drugs including Epclusa (Sofosbuvir and Velpatasvir), is occurring. Moreover, the highly chronic progression render HCV as a silent slayer for human health, and plenty of HCV cases were difficult to be timely diagnosed due to its high proportion of asymptomatic. All these indicated that HCV prevention and control are still facing severe challenges.