WASHINGTON (AP) -- Amid concerns about bioterrorism, researchers who are trying to understand how smallpox targets humans have managed to make a protein that helps the disease overcome the human immune system.

By studying this protein the researchers at the University of Pennsylvania hope to learn how smallpox defeats the immune system.

"The best defense against any virus is to understand how it functions so that we can disable it," Dr. Ariella M. Rosengard, the research team's leader, said in a telephone interview.

The university team modified the weaker vaccinia virus to help create the protein that makes its cousin, variola, so dangerous.

The work is reported in Tuesday's issue of Proceedings of the National Academy of Sciences.

There might be criticism of publishing this type of report because of concerns that it could provide information to terrorists, but "the work is far more likely to stimulate advances in vaccinology or viral therapy than it is to become a threat to biosecurity," writes P.J. Lachmann of the Centre for Veterinary Science in Cambridge, England.

Lachmann made the comments in an accompanying commentary in Proceedings.

Variola is the virus that causes deadly smallpox, but access to it is severely limited. The last case of smallpox in the world occurred in 1977 and the disease is considered to have been eliminated.

The only official stocks of variola are at the Centers for Disease Control in Atlanta and at a Russian lab. However, concern persists that clandestine stocks may have been obtained by rogue governments or terrorists.

Vaccinia is less virulent in humans and was used to vaccinate people against the more dangerous disease.

Rosengard said she had been researching the variola protein for years in an effort to understand the human immune system and how diseases overcome it. Smallpox is a good case study, she said, because it is specific to humans.

"It is effective in disabling the first line of (human) defense," she noted. Finding a way to block that could lead to a way to protect people from the disease.

Interest in her work changed sharply after the terrorist attacks Sept. 11, Rosengard noted. When anti-terrorist efforts began considering the possibility of attacks with germs it became obvious that not many people were studying smallpox.

By modifying 13 compounds in vaccinia, called nucleotides, the researchers were able to convert a vaccinia protein called "virus complement control protein" into "smallpox inhibitor of complement enzymes," or SPICE.

The smallpox version of the protein is 100 times more effective in disabling the part of the human immune system that attacks pathogens, the researchers said. It's a difference that helps make smallpox so much more dangerous than vaccinia.

By determining which changes in the protein were critical in making it more virulent, researchers hope to find ways to target and overcome the virus. The findings could be important in other diseases as well.

The SPICE protein may create an environment around infected cells that protects them from attack by the immune system while the virus reproduces in the cell, the researchers reported.

This helps point the way to treating the disease by seeking ways to disable the SPICE protein, the team said.

Copyright 2002 The Associated Press. All rights reserved.