Thursday, 13 June 2013

How HIV kills immune cells, discovered by Scientists



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. 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.

Scanning electron micrograph of HIV particles infecting a human T cell 

HIV replicates inside infection-fighting human immune cells called CD4+ T cells through complex processes which 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. 


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.


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.






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