What Really "Causes" AIDS?

As of 2012, roughly 35 million people were living with HIV worldwide, and 1.5 million died from AIDS-related illnesses in 2013.  AIDS is characterized by the death of large numbers of CD4 T cells after HIV infection.  Without a sufficient number of T cells, people with AIDS succumb to otherwise harmless viral and bacterial infections.

It’s true that HIV causes AIDS.  However, until now, researchers did not understand exactly how large numbers of T cells were killed by the virus, resulting in AIDS.  According to Gilad Doitsh, staff research investigator at the Gladstone Institute of Virology and Immunology, “the fundamental ‘killing units’ of CD4 T cells … are other infected cells, not the free virus”. 

T cells can become infected by HIV in two ways, by free-floating virus particles or through cell-to-cell transmission.  During cell-to-cell transmission, a previously infected T cells passes the virus to a neighboring cell.

Researchers at Gladstone knew that quiescent, resting T cells are unable to support productive HIV infection.  They showed that when resting T cells become infected by cell-to-cell transmission, viral DNA accumulates in the cell, triggering cell death.  This viral DNA is sensed by the interferon gamma inducible protein 16 (IFI16) that activates the caspase-1 pathway, leading to a form of programmed cell death known as pyroptosis.  When the researchers inhibited cell-to-cell transmission by disrupting contact between cells, they prevented T cell death.  The group published their findings in Cell Reports.

These findings reveal new approaches to AIDS therapy that could be used in conjunction with traditional anti-retroviral treatments.  According to Warner C. Greene, director of the Gladstone Institute of Virology and Immunology, “by preventing cell-to-cell transmission, we may be able to block the death pathway and stop the progression from HIV to AIDS”.



Sources: Cell Reports, Science Daily, CDC