Hepatitis C Study May Lead to New Treatments

Every year, hepatitis C kills up to 10,000 Americans and costs $600 million in health care expenses and lost wages.¹ Most people who are infected develop chronic liver disease, cirrhosis, or liver cancer. Treatments for the disease usually fail, which is why finding new ways to target the virus is so important.

Dr. Joachim Frank of New York's Wadsworth Center led a research group that showed how the hepatitis C virus takes over a host cell's protein-making machinery, known as the ribosome, and forces it to churn out viral proteins for constructing more virus particles.² This eventually kills the host cell and allows the spread of the new virus particles to other cells. Using a cryo-electron microscopy technique that he pioneered, Dr. Frank and his group captured the first image of viral genetic material bound to a ribosome and poised to trigger protein synthesis. The image revealed that the end of the virus' genetic material twists into a hook that snags the host's ribosomes. This viral hook forces the ribosomes to change shape dramatically, ensuring that they crank out viral proteins rather than host cell proteins.

By providing a clear view of how hepatitis C commandeers cell machinery in an infected host, the work may point to new molecular targets for drugs to treat the disease. Other viruses--such as those that cause polio, foot-and-mouth disease, and a type of herpes--are thought to use similar infection strategies. A better understanding of how hepatitis C infects cells may also advance efforts to design drugs to treat these viruses. More generally, the work improves our understanding of how proteins are made--a cellular process essential for all life.

REFERENCES

¹Recommendations for prevention and control of hepatitis C virus (HCV) infection and HCV-related chronic disease. MMWR 1998; 47(No. RR-19): 1-33.

²Spahn CMT, Keift JS, Grassucci RA, Penczek PA, Zhou K, Doudna JA, Frank J. Hepatitis C virus IRES RNA-induced changes in the conformation of the 40S ribosomal subunit. Science 291:1959-62, 2001.

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