DNA editing tools can be used to combat herpes viruses, Dutch scientists have shown.
The herpesvirus family includes EBV, which causes glandular fever, varicella zoster, which causes chickenpox, and HSV, which causes cold sores and genital lesions, and nearly everybody is infected with at least one of these agents.
The herpes family is so successful because these agents have evolved to persist in the body for the lifetime of the infected individual.
The viruses lurk in the form of small pieces of DNA that park themselves alongside our own human DNA inside our cells. This places them beyond the reach of the immune system and makes them very hard to combat with drugs.
Now, Robert Jan Lebbink and his colleagues, from the University Medical Centre Utrecht, have shown that it might be possible to employ a recently-discovered DNA editing tool called CRISPR/Cas to selectively chop up and deactivate the viral DNA hiding inside our cells while leaving the host (human) DNA untouched.
CRISPR was discovered in bacteria which use it to protect themselves against viral infections. It works like a pair of molecular scissors, which slide along a strand of DNA looking for a particular sequence of genetic information.When this is encountered, the DNA is cut apart at that point.
Writing in PLoS Pathogens, the Utrecht team reasoned that it might be possible to use the CRISPR system to probe cells for sequences unique to herpes virus and destroy the integrity of the viral DNA, rendering the infection inviable.
Working with cultured cells, the team have tested the approach against three different herpes viruses. Epstein Barr Virus (EBV) causes glandular fever and is also linked to certain forms of cancer, including lymphoma and nasopharyngeal carcinoma.
A single CRISPR construct recognising a key part of the EBV DNA was able to deactivate the virus in 40-60% of cells harbouring EBV infection. When two different CRISPRs, each targeting slightly different parts of the EBV DNA, were used simultaneously the viral deactivation rate rose to more than 95%.
The approach was similarly effective against another common herpes virus called CMV - cytomegalovirus - which can cause fatal infections in patients with weakened immune systems, particularly transplant recipients.
However, the team did notice that, unless they attacked CMV from multiple angles at once using a range of CRISPRs targeting several genes known to be essential to the virus, they quickly saw the emergency of resistant viruses capable of side-stepping the therapy.
Another herpes virus with which many people are miserably familiar is the herpes simplex virus, which causes recurrent infectious cold sores and genital lesions.
The CRISPR technique completely blocked the growth of the virus in cultured cells. However, it was not effective against the dormant virus.
In humans, herpes simplex viruses hide in the nervous system in a state of deep slumber, and this may explain why the treatment was unsuccessful in this instance.
The inactive state of the viral DNA might have rendered it inaccessible to the CRISPR machinery.
But the team have tested only a limited set of DNA targets on the virus so far, meaning that it may just be a question of finding the sweet spot where the virus remains vulnerable. If they can, it may finally usher in a means to end the misery for millions who suffer frequent, unsightly and painful outbreaks, by editing out their herpes infection...