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Anti-HIV mutation poses hepatitis risk.

A genetic mutation that protects people from AIDS might also make them susceptible to hepatitis C, a new study finds. The mutation, designated as delta-32 in a gene called CCR5, occurs in 1 percent of whites. The mutation helps people resist infections by human immunodeficiency virus, which causes AIDS.

Researchers in Germany compared three groups: 153 hepatitis C patients, 102 HIV-positive patients, and 130 people who had both infections.

Although some in the HIV-Infected group and the doubly-infected group had inherited a copy of the mutation from one parent, none had received a copy from each parent. But 12 of the 153 people with only hepatitis C, nearly 8 percent, had received a delta-32 mutation from both their parents, report Rainer P. Woitas and his colleagues at the University of Bonn.

Blood tests showed that single-mutation carriers turned up in an equal proportion, about 17 percent, in the HIV-only and hepatitis C-only groups. A slightly higher proportion of the doubly infected people carried a single copy of delta-32.

One way HIV attacks the immune cells known as CD4 T cells is by binding to the protein encoded by CCR5. Multiple copies of this so-called CCR5 receptor sit on the surface of each CD4 T cell. If the gene is mutated, the cells produce a defective receptor protein and HIV can't enter the cell.

However, CCR5 receptors aren't just the doors through which HIV enters CD4 T cells. Their main job is to enable CD4 T cells to work with other immune system agents to help direct attacks on viruses and other pathogens. Indeed, among the people with hepatitis C in this study, those who inherited the mutation from both parents had hepatitis C viral loads 3 to 5 times as high as those in people without the mutation, Woitas says.

Although researchers don't know the precise mechanism by which CCR5 receptors influence the immune response against hepatitis C, Woitas says it "is reasonable that this mutation ... should alter the signaling" of immune agents. Studies of mice indicate that the supply of cytokines--proteins that orchestrate immune responses--goes out of balance in the presence of defective CCR5 receptors.

Other studies have linked the delta-32 mutation with a high incidence of asthma, another indication that altered CCR5 receptors disrupt the immune system.

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Title Annotation:hepatitis C
Publication:Science News
Article Type:Brief Article
Date:Feb 24, 2001
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