Fransisco, United States has 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. 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 and related conditions.
Two separate journal articles, published simultaneously in
Nature and Science, detail the research from the laboratory of
Warner C. Greene, MD, PhD, who directs virology and
immunology research at Gladstone, an independent
biomedical-research non-profit.
His laboratory'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 the Nature paper, 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. The Nature
paper further describes laboratory tests in which an existing
anti-inflammatory inhibits caspase-1, thereby preventing pyroptosis and breaking the cycle of cell death and inflammation.
"Gladstone has made two important discoveries, first by showing 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 Robert F. Siliciano, MD, PhD, 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 laboratory has been able to identify a potential
new therapy for blocking the disease's progression and
improving on current antiretroviral medications." The
research comes at a critical time, as so-called AIDS fatigue
leads many to think that HIV/AIDS is solved. In fact, HIV
infected an additional 2.3 million people last year, according
to UNAIDS estimates, bringing the global total of HIV-
positive people to 35.3 million. Antiretroviral medications
(ARVs) can prevent HIV infections from causing AIDS, but
they do not cure AIDS. Further, those taking ARVs risk both
a latent version of the virus, which can rebound if ARVs are
discontinued, and the premature onset of diseases that
normally occur in aging populations. Plus, some 16 million
people who carry the virus do not have access to ARVs,
according to World Health Organization estimates.
Seeking solutions for all these challenges, the new Gladstone
discovery builds on earlier research from Dr. Greene's lab,
published in Cell in 2010. This study showed how HIV attempts, but fails, to productively infect most of the immune system's CD4 T cells. In an attempt to protect the body from the spreading virus, these immune cells then commit "cellular suicide," leading to the collapse of the immune system — and AIDS.
After that research, the Gladstone scientists began to look for
ways to prevent this process by studying exactly how the
suicidal response is initiated. Working in the laboratory with human spleen and tonsil tissue, as well as lymph-node tissue from HIV-infected patients, the researchers found that these so-called abortive infections leave fragments of HIV's
DNA in the immune cells. As described in Nature, pyroptosis
ensues as immune cells rupture and release inflammatory
signals that attract still more cells to repeat the death
cycle.
Via: Nigerian Tribune
No comments:
Post a Comment