Scientist at the Gladstone Institutes have
identified the precise chain of molecular events
in the human body that drives the death of most
of the immune system’s CD4 T cells as an HIV
infection leads to AIDS.
“Gladstone has showed how the body’s own
immune response to HIV causes CD4 T cell
death via a pathway triggering inflammation,
and secondly by identifying the host DNA
sensor that detects the viral DNA and triggers
this death response,” said Dr. Robert F.
Further, they have identified an existing anti-
inflammatory drug that in laboratory tests
blocks the death of these cells — and now are
planning a Phase 2 clinical trial to determine if
this drug or a similar drug can prevent HIV-
infected people from developing AIDS.
Two separate journal articles, published
simultaneously in Nature and Science, detail the
research from the laboratory of Dr. Warner C.
Greene, who directs virology and immunology
research at Gladstone, an independent
biomedical-research nonprofit.
His lab’s Science paper reveals how, during an
HIV infection, a protein known as IFI16 senses
fragments of HIV DNA in abortively infected
immune cells. This triggers the activation of the
human enzyme caspase-1 and leads to
pyroptosis, a fiery and highly inflammatory form
of cell death.
As revealed in Nature, this repetitive cycle of
abortive infection, cell death, inflammation and
recruitment of additional CD4 T cells to the
infection “hot zone” ultimately destroys the
immune system and causes AIDS.
Siliciano, a professor of medicine at Johns
Hopkins University, and a Howard Hughes
Medical Institute investigator. “This one-two
punch of discoveries underscores the critical
value of basic science — by uncovering the
major cause of CD4 T cell depletion in AIDS, Dr.
Greene’s lab has been able to identify a potential
new therapy for blocking the disease’s
progression and improving on current
antiretroviral medications.”
