Patrick Guilfoile: How HIV kills — surprises after 30 years
HIV continues to be a major health threat, causing 70 million new infections each year, and 3.5 million deaths across the world.
HIV has been the world’s most intensely studied pathogen since its discovery over 30 years ago.
Yet there are many things we still don’t know about it, including the details of how the virus destroys the immune system.
This collapse of the immune system ultimately leads to death from secondary infections (AIDS).
Consequently, our limited knowledge of the interaction of the virus and the immune system has hampered the development of an effective vaccine, and limited targets for treating HIV infection.
New research by scientists at several Universities and Institutes in California is shedding new light on how HIV destroys the immune system.
This may ultimately lead to additional treatments and new approaches to vaccination.
From the start of the HIV epidemic, it was clear that the virus knocks out the immune response by killing a central gatekeeper cell (CD4 T-cells).
These cells regulate key aspects of our response to many pathogens, and we become susceptible to many normally harmless microbes (like Baker’s yeast) when the virus destroys these critical cells.
Although it was clear that HIV killed these cells, it wasn’t exactly clear how it did so.
Typically, HIV can infect only a small fraction of these gatekeeper cells, so there was uncertainty how it could wipe them all out.
Researchers conducted a series of experiments with gatekeeper cells isolated from human tonsils.
Initially, they added a piece of HIV DNA to proteins from these cells, and identified a protein that clung to the HIV DNA.
When activated by HIV DNA, this human protein causes cells to self-destruct.
This HIV-catalyzed cell destruction in turn causes more T-cells to move into the area and these cells, in turn, are killed through HIV infection or through HIV causing the cells to self-destruct.
This work is an important advance in our understanding about how HIV kills gatekeeper cells it can’t infect. This, in turn, may lead to new treatment methods that target the human protein that triggers cell death.
This improved understanding of the interplay of the virus and the immune system may also contribute to the bank of knowledge needed to develop an effective vaccine.
More information is available in the article by Monroe et al. “IFI16 DNA Sensor is Required for Death of Lymphoid CD4 T Cells Abortively Infected with HIV” Science 343- 428-432, January 24, 2014.
PATRICK GUILFOILE has a doctorate in bacteriology and is the associate vice president at Bemidji State University.