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Protein from the wrong side of the tracks aids cancer virus

sciences and of molecular virology, immunology and medical genetics, and a Comprehensive Cancer Center researcher.

"Our study is the first to show that this novel protein is important for survival of the virus, which suggests that a drug that targets it might disrupt viral replication and provide a new therapy for infected people."

Some 15 to 25 million people are infected with HTLV-1 worldwide, and 1 to 4 percent of them will eventually develop adult T-cell leukemia or lymphoma, a cancer that responds poorly to treatment and that can cause death within six months. In others, it causes a crippling and painful autoimmune-like disorder, tropical spastic paraparesis.

For this study, Green and his collaborators first looked at how loss of the HBZ protein affected the virus's ability to infect and survive in its normal host immune cell, human T lymphocytes, or T cells, growing in culture.

They found little difference between the HBZ mutant HTLV and the normal virus. Both infected the cells and immortalized them equally well.

(Normally, T cells in culture die within a week or two. When the same cells are infected with HTLV-1, however, the virus causes changes that extend their life span indefinitely.)

Next, the scientists tested the ability of the mutant virus to infect and persist in a rabbit model, one of the few animals that duplicates human HTLV-1 infection. Those results indicated that the HBZ protein was required for prolonged infection in the body.

After eight weeks, rabbits that were infected with virus that lacked HBZ had one to 10 copies of the virus per 1,000 lymphocytes, whereas rabbits infected with normal virus had 50 to 100 HTLV-1 copies per 1,000 lymphocytes.

The virus may not survive well without HBZ because the immune system readily destroys cells infected by these viruses, Green says.

"We believe that HBZ acts as a brake on viral replication," he says. "Without HBZ, the vir
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Contact: Darrell E. Ward
Darrell.Ward@osumc.edu
614-293-3737
Ohio State University
8-Jun-2006


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