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Cancer drug slows poxvirus in mice

Mice given a relatively new cancer drug can survive an otherwise lethal dose of vaccinia virus, a relative of smallpox virus, report scientists supported by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. The findings, say the investigators, suggest that Gleevec or similar drugs might be useful in preventing adverse side effects of smallpox vaccine. The classic smallpox vaccine is made from live, weakened vaccinia virus and is not recommended for people with compromised immunity, except in emergency situations where they may have been exposed to smallpox virus.

"This study helps illuminate the cellular machinery used by poxviruses to exit infected cells, and also provides new support for the concept of treating viral infections by targeting specific host cell molecules rather than the viruses themselves," says NIAID Director Anthony S. Fauci, M.D.

The senior author of the paper, published online this week in the journal Nature Medicine, is Daniel Kalman, Ph.D., of Emory University School of Medicine in Atlanta.

Like all viruses, poxviruses co-opt various cellular molecules and processes to enter a cell, replicate and then spread to uninfected cells. Using lab-grown cells, Dr. Kalman and his colleagues identified specific cell proteins vaccinia uses to detach from an infected cell and move toward an uninfected cell. The proteins, members of the Abl-family (pronounced "able") of tyrosine kinases, are well known to cancer investigators because mutation of one family member, Abl, causes a rare form of cancer known as chronic myelogenous leukemia (CML). Gleevec inhibits Abl-family tyrosine kinases and has proved very useful in treating CML.

To learn whether Gleevec could prevent or lessen vaccinia's ability to spread in a living organism, the researchers treated mice with either saline solution or with Gleevec at a dose equivalent to that given to humans being treated for CML.
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Contact: Anne A. Oplinger
aoplinger@niaid.nih.gov
301-402-1663
NIH/National Institute of Allergy and Infectious Diseases
27-Jun-2005


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