Mice given Imatinib 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 Glevec ( Imatinib ), 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.
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The senior author of the paper is Daniel Kalman, Ph.D., of Emory University School of Medicine in Atlanta.

The study is published in the journal Nature Medicine.

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, 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 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 ).
Imatinib inhibits Abl-family tyrosine kinases and has proved very useful in treating CML.

To learn whether Imatinib could prevent or lessen vaccinia's ability to spread in a living organism, the researchers treated mice with either saline solution or with Imatinib at a dose equivalent to that given to humans being treated for CML.
Next, they exposed the mice to ordinarily lethal amounts of vaccinia.
All of the Imatinib-treated mice survived, while 70 percent of the untreated mice died.

This finding, if confirmed in additional animal model studies, suggests that Imatinib might play a role in addressing a public health emergency in the event of a smallpox outbreak, Kalman says. Specifically, Imatinib might be useful as a preventative against adverse effects of smallpox vaccine, enabling clinicians to use the vaccine even in people who otherwise could not take it.
Given for a short period, Imatinib theoretically could hamper the cell-to-cell spread of virus and allow the body's immune system to mount a successful defense, he explains.

Experiments to test whether Imatinib might work against smallpox virus as well as against vaccinia virus are now being planned, Kalman says.

" The approach of fighting disease by targeting drugs to cellular molecules rather than to disease agents themselves may be applicable to a wide variety of pathogenic microorganisms," he says.

Source: National Institutes of Health, 2005


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