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Peptide targets latent papilloma virus infections

By Robert Sanders, Media Relations | 02 January 2007

BERKELEY – While a newly marketed vaccine promises to drastically reduce human papilloma virus (HPV) infections, the major cause of cervical cancer, a new discovery by University of California, Berkeley, researchers could some day help the millions of people already infected and atconstant risk of genital warts and cancer.

One study found that 75 percent of sexually active men and women under 50 have, or have had, an HPV infection, while 10,000 women annually develop cervical cancer, more than 90 percent of which is caused by HPV. Four thousand women die of cervical cancer each year.



In upper photo, the chromosomes of a dividing epithelial cell (red) have more than ahundred hitchhikers — DNA plasmids of the human papilloma virus (green). Treating a cell with a special peptide created by UC Berkeley researchers kicks the hitchhikers off (lower photo), and could lead to a drug that will prevent spread of the virus. (Photos courtesy Botchan lab/UC Berkeley)

Once infected, it's difficult to rid oneself of the virus because it hides as a latent DNA in cells ofthe epithelial tissue, such as skin and the lining of the vagina and cervix, and spreads as these cells divide.

The UC Berkeley team created a protein fragment, or peptide, that successfully prevents the virus from hitching a ride on a cell's chromosomes as the cell divides. If such a peptide - or more likely, a drug that mimics the action of the peptide - works in the body, it wouldeffectively stop the virus from spreading or generating warts, which can progress to cancer.

"We're optimistic that this will work generally for many different genetic variants of human papilloma virus, though it's too early to say how many of the genotypes of this virus will respond," said Michael Botchan, professor of molecular and cell biology and a faculty affiliate of the UC Berkeley branch of theCalifornia Institute for Quantitative Biology (QB3). "The hope is to have one drug that works for all different human virus types."

"The second most preventable cancer in the world, after lung cancer, is cervical cancer, the result of high HPV infection rates in the developing world, in Asia and South America and Africa," he added. "If we can get something to stop HPV replication, it wouldhave a big health impact."

Botchan, post-doctoral fellow Eric A. Abbate and researcher Christian Voitenleitner reported their results in the Dec. 28 issue of the journal Molecular Cell.

Many of the 90-plus known genetic variants or strains of HPV cause warts in surface tissues, including the penis, vagina and cervix, but three variants - HPV-16, 18 and 31 - are notorious as the primary causesof cervical cancer in the world. The virus hides out in epithelial stem cells, which are naïve cells at the base of the skin that can turn into many of the various types of cells that make up the skin. As these cells divide and differentiate into skin cells, the viruses hitch a ride on the cells' chromosomes but do not become part of the chromosomes, as do other known pathogens, such as HIV inblood cells.

The virus can transform infected cells and make them proliferate into nipple-like warts. Unlike unsightly warts on the skin, tongue or penis, warts in the cervix are often flat and easily overlooked unless laboratory staining is used to find signs of pathology, as in Pap screening. If untreated or left to flare up repeatedly, the warts can progress to cancer.

Earlier work by Botchanand numerous other researchers on the human and cow (bovine) papilloma virus has shown how the virus moves into new cells. It carries its genes in the form of a circular DNA plasmid that nestles in the nucleus of the cell and makes use of the cellular machinery to generate more copies of itself. Each cell can house hundreds of plasmids.

When the cell divides into two daughter cells, the...
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