14 DAY TRIAL // For a while now, researchers have been wandering how come HIV kills T cells, when most of them seem to be 'bystander' cells, that are not productively infected, and have now found a reasonable explanation.
The death of CD4 T cells is what marks the progression of the HIV virus to fully developed AIDS, and the majority of these cells are contained in the lymphoid tissues, including the spleen and tonsils.
These are actually the places where HIV reproduces the most and the researchers found that these dying cells are not simple bystanders.
Warner Greene of The Gladstone institute for Virology and Immunology in San Francisco said that “in [infected] primary human tonsils and spleens, there is a profound depletion of CD4 T cells.
“In tonsils, only one to five percent of those cells are directly infected, yet 99 percent of them die.”
The HIV virus does infect these cells, and even though it is unable to replicate, it triggers the immune response that will eventually kill the cells.
Greene and his colleague Gilad Doitsh explain that once the virus infects the CD4 T cells, it starts copying its RNA into DNA.
Normally, the sick cells should replicate, but apparently this doesn't happen this way, as the process of RNA copying remains incomplete in some cells, and once they realize what's happening, in order to protect themselves, they commit some kind of suicide.
These cells don't die like they normally would; instead, they produce ingredients that are the sign of inflammation and break open, spreading their contents – this finding could be the missing link between HIV and the inflammation that usually comes with it.
Greene said that “that inflammation will attract more cells leading to more infection; it's a vicious cycle.”
There is, however, a way of saving these cells, and the researchers used an array of HIV drugs that act at several points in the viral cycle, to find out how.
They reported that drugs which blocked the viral entry or that prevented reverse transcription altogether stopped the CD4 T cell killing.
On the other hand, drugs that act later in the cell's life cycle to prevent reverse transcription after it has already begun, did not manage to prevent cell death.
To conclude, even if the death of CD4 T cells is a normal response in order to protect the host, it actually compromises the entire immune system.
But Greene explained that all the available varieties of anti-HIV drugs will still work to prevent the spreading of the virus and to reduce the viral load, thus fighting the infection.
This new research could lead to new treatment strategies, like developing drugs that act on the cell sensor that triggers the immune response, and preventing CD4 T cells' death.
The researchers report their findings in studies of human tonsils and spleens in the November 24th issue of Cell – a Cell Press publication.