In a discovery that may open a new front in the war on AIDS, government scientists have isolated a protein that the AIDS virus needs to launch its deadly attack on cells.
Writing in today's issue of the journal Science, researchers at the National Institute of Allergy and Infections Diseases say they have found a protein, which they call fusin, that must be present for the AIDS virus to infect white blood cells, the primary target of the virus.The discovery was said by other scientists to be a significant milestone in AIDS research that eventually could lead to new drugs and vaccines against HIV, the virus that causes AIDS.
Edward A. Berger, leader of the team that made the discovery, said the finding will have no immediate impact on people infected with HIV, but it does answer a question that has confounded researchers for 10 years and slowed the search for a cure.
HIV attacks cells in the bloodstream that have on their surface a molecule called CD4. HIV uses CD4 to fuse with the target cell. But researchers discovered that CD4, by itself, was not enough. Some other receptor on the cell surface had to be present for the HIV infection to occur.
Fusin is that second receptor, Berger said. He said the finding was "a major new insight into how HIV gets into cells and suggests some things we weren't even considering about how HIV causes disease."
"This is very significant basic research that helps to solve the puzzle of how HIV gets into cells," said John Moore, an AIDS researcher at the Aaron Diamond AIDS Research Center in New York. "There has been very intensive efforts by many labs to find this. Many people have given up."
Robert Gallo of the University of Maryland, the co-discoverer of the HIV virus, said the research represented "one of the milestones in AIDS research. This opens new doors for therapy and for developing vaccines."
Other labs have confirmed the finding, but their work has not yet been published.
Berger and his colleagues found fusin by genetically altering a laboratory virus, called vaccinia, to resemble HIV and to cause a cell to turn blue if it fuses with the virus.
They then exposed this laboratory virus to cultured mouse cells that had been altered to include the human CD4 gene, along with selected genes for other molecules found on the surface of human cells.
Through a painstaking process of elimination, the researchers eventually isolated fusin and identified it as the protein that is a co-factor with CD4 in the HIV infection process.
To prove the role of the protein, CD4 cells with and without fusin were exposed to HIV from blood samples. Only the cells with fusin became infected. Researchers then developed an antibody against fusin and found that laboratory cultures protected by the antibody could not be infected by HIV.
Berger said fusin does not play a role in the HIV infection of macrophages, another type of blood cell also attacked by HIV. This suggests, he said, that there is a separate molecular co-factor for the macrophage infection.