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NIH Scientists Discover How HIV Kills Immune Cells

Findings have implications for HIV treatment (June 5)

Untreated human immunodeficiency virus (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. Scientists at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), have discovered 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, the scientists say.

The new study will be published in Nature.

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 were surprised to discover that the DNA breaks during HIV integration activate DNA-PK, which then performs an unusually destructive role: eliciting a signal that causes CD4+ T cells to die. The cells that succumb to this death signal are the 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 prevents 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.

Source: NIAID; June 5, 2013.

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