CRISPR Cuts Out HIV

Could a bacterium’s defense against bacterial viruses be used to protect a human cell from HIV?

A lot is in the news about people who seemed to be “cured” of HIV (the virus causing AIDS) yet two years later, the virus returns. That’s because the HIV virus hides a DNA copy of its RNA within the human cell’s own DNA chromosomes. The latently infected cells circulate in the bloodstream, undetected, because the hidden viral DNA looks the same as host DNA, to the immune system.

But what if we could cut the embedded DNA copy of HIV’s genome–out of the host cell DNA?

Amazingly, a way to do that has been reported, using a molecular machine used by bacteria to defend themselves from bacterial viruses. This defense is called CRISPR (clustered regularly interspaced short palindromic repeats). It is named for the clusters of short repeated sequences that appear in DNA of the bacterium. Each short sequence has been copied from the viral genome of a previously infecting virus. The genome of the previously infecting virus got recognized by the CAS complex–a protein/RNA machine that makes RNA copies of the infecting DNA sequence. The CAS RNA copies then cause the cell to (1) degrade the viral genomic DNA; (2) make short copies of viral sequence and insert them into host. These short copies (the “palindromic repeats” of CRISPR) then serve to generate future CAS RNAs that recognize the virus when it infects again–a kind of bacterial immune system.

For biotechnology, the CAS machine turns out to be an amazing way to edit vertebrate genomes. We can cut out a gene, for example a cancerous gene. So now, the PNAS researchers report using CAS to edit a small part of an integrated HIV genome, and prevent the integrated viral sequence from generating new phage particles. So far, this has been done in tissue culture. It will remain to be seen whether a delivery method can enable use of CRISPR/CAS to prevent HIV virus production in humans.