SAN FRANCISCO, Aug. 27 (UPI) -- Researchers have found that the progression to acquired immunodeficiency syndrome, or AIDS, after human immunodeficiency virus, or HIV, infection is caused not by the virus's direct effect on immune cells, but by the effect of infected immune cells on other immune cells.
The discovery changes the approach to treating HIV, as researchers now think they have a method to block the progression from virus to AIDS based on this new understanding of how the infection works.
"Although free-floating viruses establish the initial infection, it is the subsequent cell-to-cell spread of HIV that causes massive CD4 T cell death," says co-first author Nicole Galloway, PhD, a post-doctoral fellow at the Gladstone Institute of Virology and Immunology. "Cell-to-cell transmission of HIV is absolutely required for activation of the pathogenic HIV cell-death pathway."
A previous study found that 95 percent of cell death from HIV is caused by cells committing suicide after a failed effort at infection. Cells that are "at rest" abort the virus when it attempts to invade them, however DNA is left behind when HIV is ejected from cells. Enzymes in the cell are activated by this DNA, which causes them to commit defensive suicide.
While HIV can infect new cells as a free-floating virus in the body, the way it spreads most successfully is through this cell-to-cell transmission -- which researchers confirmed in the new study, published in Cell Reports.
The researchers tested several methods of HIV transfer: genetically modifying the virus; applying chemical HIV inhibitors; blocking inter-cellular synapses; and increasing the physical distance between the cells so they could not come into contact with one another. The tests showed that the pro-inflammatory death of cells caused by HIV was disrupted, also halting cellular suicide.
"This study fundamentally changes our mindset about how HIV causes massive cell death, and puts the spotlight squarely on the infected cells in lymphoid tissues rather than the free virus," said Dr. Warner C. Greene, director of the Gladstone Institute of Virology and Immunology. "By preventing cell-to-cell transmission, we may able to block the death pathway and stop the progression from HIV infection to AIDS."