Genes boost hepatitis C defenses

Researchers from the Johns Hopkins University, the U.S. National Cancer Institute, and the United Kingdom's Southampton University are one step closer in figuring out why some people spontaneously recover from hepatitis C infection: Their genes appear to unleash a faster frontline immune defense. Though the research will not benefit HCV-infected patients anytime soon, "It bring us closer to understanding how the virus works," says JHU scientist and study coauthor Chloe Thio.

About 20% of people infected with HCV--considered the most serious of a family of liver viruses--clear the virus without treatment. Around 3 million U.S. patients and 180 million people worldwide remain chronically infected and are at risk of developing liver failure or cancer. Annually, 10,000-12,000 U.S. patients die from HCV. HCV studies in chimpanzees have suggested that natural killer cells, which are continually poised to defend the immune system if a virus strikes, were more active in those that recovered. The researchers set about finding the genes involved in that immune response by analyzing the DNA of 1,037 HCV patients, of whom 352 spontaneously recovered.

Natural killer cells are kept in check by inhibitory receptors called KIRs to ensure that healthy tissue is not attacked. The scientists found a particular gene combination that controls one KIR receptor, and the molecule attached to it was twice as common in those patients who spontaneously recovered than in those chronically infected. Thio explains that when the body senses viral infection, including hepatitis, it must activate natural killer cells by turning off KIR receptors. This KIR combination appears weak, thus "it's easier to overcome," says Thio. However, only patients thought to have been infected by an initial low dose of HCV--through drug or tattoo needles instead of a blood transfusion--had the genetic protection. Thio suggests that extra virus from tainted blood simply overwhelmed those patients' first-line defenses.

In an accompanying editorial, Stanford University's Peter Parham says other factors also contribute to spontaneous HCV recovery. But Parham notes that a type of leukemia is already treated by releasing natural killer cells from a different KIR receptor, so now doctors must figure out how a similar strategy could be used to treat HCV.

HCV is a common coinfection among HIV-positive people and is a leading cause of death among adults with AIDS. Some health officials believe HCV can sometimes be transmitted through certain sex acts, including unprotected sex, although contact with HCV-infected blood is the most common route of infection.

The full study, titled "HLA and NK Cell Inhibitory Receptor Genes in Resolving Hepatitis C Virus Infection," and commentary, "NK Cells Lose Their Inhibition," appears in the journal Science. (AP)

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