With the five-year grant from the National Institutes of Health, the IUSM scientists intend to learn how the virus is able to evade the body’s defense mechanisms against viruses and other intruders, said Cheong-Hee Chang, leader of the smallpox project.

"The potential use of smallpox as a bioterrorist agent has created a need to fully understand how this virus acts against the immune system in the development of the disease," said Chang, associate professor of microbiology and immunology.

All of the researchers involved in the project are affiliated with the Walther Oncology Center, a research center at the IU School of Medicine.

The IU researchers will make use of vaccinia virus, a relative of the smallpox virus. Vaccinia is the virus used to create vaccines that protect people against smallpox infection.

The World Health Organization announced in 1980 that smallpox disease had been eradicated. Few Americans have been vaccinated against the disease since then, and it’s unclear how much protection remains for older Americans vaccinated years ago.

Concerns have risen in recent years that a terrorist organization might gain access to a stockpile of smallpox virus and develop it into a weapon. Smallpox is a highly contagious disease, with fatality rates greater than 30 percent among those with no vaccine protection.

Chang said the IU researchers are studying how smallpox manages to disrupt the operations of important immune system components called antigen presenting cells (APCs). The APCs are among the "first-responders" of the immune system--they engulf viruses or other pathogens they encounter, breaking down the intruders into small pieces. They then "present" those pieces, in effect notifying other immune system cells that the immune system should take action against the invaders.

The vaccinia virus appears to have developed a variety of techniques that work at both the cellular and genetic levels to protect itself by disrupting the function of the APCs. The IUSM researchers have focused on four projects investigating how the virus might hide from the immune system, said Chang.

Other researchers involved in the project are: Janice Blum, professor of microbiology and immunology; Randy Brutkiewicz, assistant professor of microbiology and immunology; Soon-Cheol Hong, assistant professor of microbiology and immunology; Mark Kaplan, assistant professor of microbiology and immunology; and Michael Klemsz, associate professor of microbiology and immunology.