Treat HIV by making cells self-destruct, says study
Scientists have proposed treating HIV infection by making infected cells self-destruct.
They say that blocking a protein that lets the virus infiltrate our DNA could be an alternative to trying to kill the virus.
Not only would the approach work against drug-resistant strains of HIV, it would also discourage future drug resistance, says the team led by Mark O'Connor at UK-based KuDOS Pharmaceuticals.
O'Connor's team, whose findings were published online yesterday (17 April) by the journal Nature Cell Biology, focused on a protein that repairs damaged DNA in human cells.
The HIV virus takes advantage of the repair operation to integrate its own DNA into the human cell's DNA. This ensures that the virus will replicate and continue to infect the patient.
If this process were stopped — by eliminating or blocking a key repair protein — the infected host cell would die, killing the virus as well.
The researchers tested whether blocking a repair protein called ATM would cause infected cells to die early. ATM is not essential for the host cell's survival.
They found that HIV did not replicate well in mouse and human cells that lacked ATM. These cells also died much more quickly than those with the protein.
The finding suggests that molecules that stop ATM from working could be used as a treatment for HIV infection.
Killing off infected cells should in theory not be harmful to patients, says René Daniel of Thomas Jefferson University, United States. Although not involved in O'Connor's study, Daniel proposed targeting DNA repair proteins in 1999 and identified ATM as a potential target in 2001.
Daniel says the approach would stop the spread of the infection, and that the immune system seems able to replace the dead cells after standard anti-HIV therapy.
Other HIV/AIDS scientists are sceptical.
Vicente Planelles from the University of Utah School of Medicine, United States, told SciDev.Net that he does not think ATM is as important as O'Connor's research implies.
Planelles published a paper earlier this year showing that ATM is not necessary for the HIV virus to integrate human DNA efficiently.
He says further experiments would be needed "to firmly establish that [ATM is] the 'active ingredient'" of the inhibition of HIV that O'Connor's team saw.
He adds that blocking ATM was not trivial because people who naturally lack it "pay a high price": they are more susceptible to cancers and having weakened immune systems.
Reference: Nature Cell Biology (published online DOI: 10.1038/ncb1250)