Three researchers who identified the hepatitis C virus won this year's Nobel Prize in Physiology or Medicine. Harvey Alter uncovered the first hints of the virus; Michael Houghton identified the virus; and Charles Rice confirmed that it caused hepatitis C.

This year's Nobel Prize in Physiology or Medicine recognizes three scientists who discovered the hepatitis C virus (HCV): Harvey Alter, MD, of the NIH; Michael Houghton, PhD, of the University of Alberta in Canada; and Charles Rice, PhD, of Rockefeller University in New York, NY. Their work has led to the development of screening tests and treatments that have dramatically reduced the incidence of hepatitis C infections worldwide and may one day eliminate the virus, a major risk factor for hepatocellular carcinoma.

“I cannot overemphasize the impact that the discovery of hepatitis C had,” says Augusto Villanueva, MD, PhD, of the Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai in New York, NY, who wasn't connected to the prizewinning research.

“One nice thing about this research is how it spans from a clinical observation to a basic virology study,” says Tim Greten, MD, of the NCI's Center for Cancer Research Liver Cancer Program.

Alter made the clinical observation in the 1970s, when he was working to reduce hepatitis transmission through transfusions. At the time, improvements in donor selection and testing for the hepatitis B virus had slashed the transmission risk, but about 10% of recipients were still contracting hepatitis. In 1975, Alter and colleagues reported that 22 surgical patients who developed hepatitis after receiving transfusions tested negative for the hepatitis A and B viruses, suggesting a third disease-causing virus (N Engl J Med 1975;292:767–70). The scientists then found that blood from patients with this mysterious form of hepatitis could induce the illness in chimpanzees (Lancet 1978;311:459–63).

However, the virus proved elusive until the 1980s, when Houghton and a team that included his colleagues Qui-Lim Choo, PhD, and George Kuo, PhD, took a chance on a novel approach. They isolated pieces of RNA and DNA from infected chimpanzees and used them to make a library of DNA fragments.

To find out if any of these snippets derived from the virus, the researchers inserted each fragment into bacteria that produced the DNA-encoded protein. Then, they added serum from an infected patient—which they surmised would harbor antibodies that would latch onto viral proteins—to the bacterial colonies. They tested more than 1 million such colonies but found only one producing a viral protein, indicating that the DNA fragments these bacteria received represented a portion of the pathogen's genome (Science 1989;244:359–62).

“The isolation of the virus was a tremendous achievement with the technology of the time,” says Villanueva.

In the 1990s, Rice and his colleagues answered the lingering question of whether the virus needed help from other pathogens to cause disease. That was a concern because researchers noticed that the viral clones they created in the lab did not spur cells to produce new virus particles in culture. Rice and his team found that the viral RNAs tested were missing a section from one end and had accrued mutations that might hamper their replication (Science 1997;277:570–4). The scientists revealed in 1997 that when they “corrected” these defects, the viral RNA induced hepatitis C in chimps, confirming that the virus acted alone.

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Artist's rendering of hepatitis C infection, a major risk factor for hepatocellular carcinoma.

Identification of HCV enabled researchers to design screening tests that have nearly eliminated it from the blood supply in many countries. Pharmaceutical companies have also introduced antiviral drugs, such as the combination of sofosbuvir and velpatasvir (Epclusa; Gilead), that can cure the illness in 95% of patients.

Although researchers haven't developed a vaccine against hepatitis C, the World Health Organization aims to stamp out the disease globally by 2030 through screening and treatment. If that effort succeeds, “it would be amazing that in less than 50 years we were able to isolate the virus and eliminate the disease,” remarks Villanueva. –Mitch Leslie

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