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New papillomavirus target could lead to specific antiviral drugs for precancerous cervical lesions

all molecules.

Human papillomavirus is a leading cause of sexually transmitted diseases in the United States. Though the genital warts resulting from such infections might be treated with human papillomavirus-specific therapies, the real beneficiaries would be women with virus-associated precancerous lesions of the cervix, said Howley. Combined with early methods of detection such as Pap smears, human papillomavirus specific antivirals could lower the rate of cervical cancer, currently the second most common cancer in women in this country and abroad.

"The real value of this approach for treating papillomavirus infections would be to treat precancerous cervical lesions so that they cannot establish a persistent infection and progress into cancer," said Howley.

The story of how papillomaviruses maintain infection in dividing cells got a boost in 1997 when researchers discovered that the viruses link their genetic material--a ring of DNA, or plasmid--to the host's chromosomes by means of the viral protein, E2. "What was missing is the identity of the cellular protein with which the viral protein E2 interacts," said Howley. Researchers tried a variety of genetic approaches such as expressing the E2 gene in yeast as a kind of bait for interacting partners, but the cellular half of the equation--the chromosomal tether--remained elusive.

As it turns out, E2 is an incredible multitasker. The viral protein is involved in replication, transcription, and cell growth, in addition to its tethering duties. Rather than try to isolate a single interacting partner, You decided to capture the entire package in vivo. Using a relatively new proteomic approach developed by Yoshihiro Nakatani, HMS professor of biological chemistry and molecular pharmacology at Dana-Farber Cancer Institute--she extracted E2 plus its many interacting partners and then set out to identify each member in the complex. It was during this experimental foray that she spotted B
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29-Apr-2004


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