Scientists discover how HIV kills immune cells

June 5, 2013

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 called CD4+ T cells through complex processes that include inserting its genes into . The scientists discovered that during this integration step, a 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 , 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.

Explore further: A cure for HIV could be all in the 'mix'

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

Related Stories

A cure for HIV could be all in the 'mix'

August 18, 2010

Current HIV treatments do not eradicate HIV from host cells but rather inhibit virus replication and delay the onset of AIDS. However, a new research published in BioMed Central's open access journal, AIDS Research & Therapy ...

Elite controllers block integration of HIV DNA into host genome

September 19, 2011

Alone among those infected with HIV-1, so-called elite controllers spontaneously maintain undetectable levels of viral replication even absent the benefit of anti-retroviral therapy. Now Mathias Lichterfeld of the Massachusetts ...

Discovery may help prevent HIV 'reservoirs' from forming

April 17, 2013

Researchers at Albert Einstein College of Medicine of Yeshiva University have discovered how the protein that blocks HIV-1 from multiplying in white blood cells is regulated. HIV-1 is the virus that causes AIDS, and the discovery ...

Recommended for you

Mutational tug of war over HIV's disease-inducing potential

August 23, 2016

A study from Emory AIDS researchers shows how the expected disease severity when someone is newly infected by HIV reflects a balance between the virus' invisibility to the host's immune system and its ability to reproduce.

Dormant copies of HIV mostly defective, new study shows

August 8, 2016

After fully sequencing the latent HIV "provirus" genomes from 19 people being treated for HIV, scientists at Johns Hopkins Medicine report that even in patients who start treatment very early, the only widely available method ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

yl2j
not rated yet Jun 06, 2013
Is this a apoptosis signal? could it be a defensive mechanism, albeit a destructive one, that prevents viral replication? If this process always occurs, how does the virus replicate?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.