BackStudies by US scientists suggest possibility of new HIV drug
Previous studies have established that HIV's deadly attack on CD4T cell is caused by apoptosis, commonly called cell suicide
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New Delhi: American scientists have for the first time shown how the human immunodeficiency virus (HIV) causes immune cells to self-destruct, and suggested that an enzyme that can block this process could lead to a new anti-HIV drug.
Previous studies have established that HIV’s deadly attack on its main target, the CD4T cell, is caused by apoptosis, commonly called cell suicide.
HIV infection in the body is marked by the dying of CD4T cells of the immune system, and the development of chronic inflammation which can lead to progression of Acquired Immunodeficiency Syndrome, or AIDS.
But there was a lack of understanding of several areas of HIV pathogenesis. And one of such area was why the CD4T cell self-destructed after a person was infected by the HIV.
Now, two studies by researchers from virology and immunology labs at the Gladstone Institutes in San Francisco, published in Science and Nature journals on Thursday have shed light on pyroptosis, a pathway to cell death mediated by an enzyme called caspase-1, which activates inflammation.
“The depletion of CD4T cells and the development of chronic inflammation are signature processes in HIV pathogenesis that propel disease progression.Our studies now reveal how pyroptosis provides an unexpected link between these two disease-promoting processes," said the researchers of the two studies in their paper in Nature.
“Identifying pyroptosis as the mechanism by which T-cell destruction takes place during an HIV infection, gives an opportunity for novel targets, such has caspase 1, for potential therapeutic intervention," they added.
The researchers found that VX-765, a drug developed by Vertex Pharmaceuticals in Cambridge, Massachusetts, that has been tested as a treatment in chronic epilepsy and psoriasis, efficiently blocks caspase 1 activity in these cells.
The drug has also been found in a phase II trial to be safe and well-tolerated over the six-week length of the trial.
“These findings demonstrate that a small-molecule inhibitor of caspase 1, shown to be safe in humans, suppresses CD4 T-cell death and inflammation elicited in lymphoid tissues by HIV-1," he researchers said.
“Pyroptosis is not a strategy to protect the host from productive infection," said Warner Greene, a molecular virologist at the Gladstone Institute of Virology and Immunology in San Francisco, California, and a co-author of both the latest works, in Nature journal.
“Instead, this is a pathway that actually promotes clinical progression to AIDS."
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