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Press Release

NIH Scientists Discover How HIV Kills Immune Cells: Findings Have Implications for HIV Treatment

June 5, 2013

WHAT:
Untreated HIV infection destroys a person’s immune system by killing infection-fighting cells, but precisely when and how HIV wreaks this destruction has been a mystery until now. New research by scientists at the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health, reveals how HIV triggers a signal telling an infected immune cell to die. This finding has implications for preserving the immune systems of HIV-infected individuals.

HIV replicates inside infection-fighting human immune cells called CD4+ T cells through complex processes that include inserting its genes into cellular DNA. The scientists discovered that during this integration step, a cellular enzyme called DNA-dependent protein kinase (DNA-PK) becomes activated. DNA-PK normally coordinates the repair of simultaneous breaks in both strands of molecules that comprise DNA. As HIV integrates its genes into cellular DNA, single-stranded breaks occur where viral and cellular DNA meet. Nevertheless, the scientists discovered, the DNA breaks during HIV integration surprisingly activate DNA-PK, which then performs an unusually destructive role: eliciting a signal that causes the CD4+ T cell to die. The cells that succumb to this death signal are the very ones mobilized to fight the infection.

According to the scientists, these new findings suggest that treating HIV-infected individuals with drugs that block early steps of viral replication -- up to and including activation of DNA-PK and integration -- not only can prevent viral replication, but also may improve CD4+ T cell survival and immune function. The findings also may shed light on how reservoirs of resting HIV-infected cells develop and may aid efforts to eliminate these sites of persistent infection.

ARTICLE:
A Cooper et al. HIV-1 causes CD4 cell death through DNA-dependent protein kinase during viral integration. Nature DOI:10.1038/nature12274 (2013).




 

Reader Comments:

Comment by: Chris S. (Montreal) Thu., Jul. 18, 2013 at 5:00 pm EDT
This makes sense since if there is a problem with a cells DNA it is going to kill itself to prevent the mutation from being replicated and causing a cancer (a cell that CAN'T kill itself)
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Comment by: MarilouCorver (South Africa) Tue., Jul. 16, 2013 at 4:15 am EDT
Thanks for very interesting article
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Comment by: Lisa Nanguti-Shilongo (Oshakati- Namibia) Mon., Jun. 24, 2013 at 5:33 am EDT
I always read that in the The Body that it is advisable for a n HIV positive person to start ART as soon as possible. If I understood this article well, it seems it is encouraging early treatment in case of HIV. What worries is that Doctor in Namibia are advising HIV positive people not to start ART until their are at least 300 or less. It s understandable for state patients but why are they doing it even with private patients who are prepared to pay for their medication themselves. Does this not harm the immune system of the HIV positive person when it could be helped as early as possible? I am concerned.
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Comment by: Frank (Chicago, Il.) Fri., Jun. 21, 2013 at 9:55 am EDT
This is tremendous news. I had been under the impression that that the mechanism had been fully understood. This piece alone can lead to that next break-through in treatment and even cure. I have always questioned how we might get to a point where with no for the virus to replicate why the immune system wouldn't foinally be able to succeed and beat the disease.
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