0850 GMT July 17, 2019
HIV can either be spread through free-floating virus that directly infects the host immune cells or an infected cell can pass the virus to an uninfected cell. The second method, cell to cell transmission, is 100 to 1000 times more efficient, and the new study shows that it is only this method that sets off a cellular chain reaction that ends in the newly infected cells committing suicide, Medical Xpress said.
"The fundamental killing units of CD4 T cells in lymphoid tissues are other infected cells, not the free virus," said co-first author Gilad Doitsh, PhD, a staff research investigator at the Gladstone Institute of Virology and Immunology. "And cell-to-cell transmission of HIV is required for activation of the main HIV death pathway."
In a previous investigation, the scientists discovered that 95 percent of cell death from HIV is caused by immune cells committing suicide in self-defense after an unsuccessful infection. When the virus tries to invade a cell that is 'at rest', the infection is aborted. However, fragments of viral DNA remain and are detected by the resting host cell. This triggers a domino effect in the cell's defense system, resulting in the activation of the enzyme caspase-1, which ultimately causes the induction of pyroptosis, a fiery form of cell suicide.
In the new study, it was revealed that this death pathway is only activated through cell-to-cell transmission of HIV, not from infection by free-floating viral particles. Using lymphoid tissue infected with HIV, the scientists compared cell death rates between cell-to-cell and cell-free virus transfer. They discovered that while overall rates of infection remained the same, there was significantly more CD4 T cell death if HIV was spread by infection from other cells than by free-floating virus.
"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," said co-first author Nicole Galloway. "Cell-to-cell transmission of HIV is absolutely required for activation of the pathogenic HIV cell-death pathway."