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HIV turns immune cells into suicide machines to cause AIDS

The human immunodeficiency virus turns host immune cells into suicide machines, using them to spread the virus and cause the progression from HIV to AIDS, a new study has found.

Researchers have showed that HIV does not cause acquired immune deficiency syndrome (AIDS) by the virus’s direct effect on the host’s immune cells, but rather through the cells’ lethal influence on one another.

HIV can either be spread through free-floating virus that directly infect the host immune cells or an infected cell can pass the virus to an uninfected cell.

Cell to cell transmission, is 100 to 1000 times more efficient, and the study shows that it that sets off a chain reaction causes the newly infected cells committing suicide.

“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, from the Gladstone Institute of Virology and Immunology in US.

According to a previous research, 95 per cent of cell death from HIV is caused by immune cells committing suicide in self-defence 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 defence system, resulting in the activation of the enzyme caspase-1, which ultimately causes the induction of pyroptosis, a fiery form of cell suicide.

“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, a post-doctoral fellow at the Gladstone Institute of Virology and Immunology.

To confirm this finding, the researchers perturbed viral transfer through a number of means – genetically modifying the virus, blocking inter-cellular synapses, applying chemical HIV inhibitors, and increasing the physical distance between the cells so they could not come into contact with one another.

Disruption of cell-to-cell contact effectively stopped the death of CD4 T cells.

The scientists speculate that the difference in cell death rates between the two methods of infection is due to the increased efficiency of cell-to-cell transmission.

Aborted viral DNA fragments are quickly removed during infection by cell-free HIV particles, so they are not detected by the cell’s defensive system.

However, in cell-to-cell transmission, the viral DNA fragments overwhelm cell maintenance, building up until they surpass a threshold and are detected. This then triggers caspase-1 activation and pyroptosis.

“By preventing cell-to-cell transmission, we may able to block the death pathway and stop the progression from HIV infection to AIDS,” said senior author Warner C Greene, director of the Gladstone Institute of Virology and Immunology.

The study was published in Cell Reports.