Until now, the precise way that untreated HIV infection destroys a person’s immune system has been a mystery. 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 research result has potential implications for protecting the immune systems of patients with HIV.
The scientists found that when HIV replicates and inserts its genes into the DNA of a CD4+ T cell, DNA-dependent protein kinase (DNA-PK) becomes activated. As HIV integrates its genes into cellular DNA, single-stranded breaks occur where viral and cellular DNA meet. The scientists discovered that the DNA breaks during HIV integration surprisingly activate DNA-PK, which causes the T cell to die.
These new findings suggest that treating HIV-infected individuals with drugs that block early steps of viral replication may improve CD4+ T-cell survival and immune function.