A technique to reversibly disrupt viral proteins is reported online this week in Nature Methods. It will allow for the study of viral protein function, a prerequisite for the design of antiviral substances, such as drugs or antibodies.
The study of viral genes essential for infection is difficult because strains with deletions or mutations in these genes fail to grow. Martin Messerle and colleagues have tackled this problem not at the level of the gene but at the protein level. They adapt a method originally developed to induce protein instability in mammalian cells, to the large family of herpes viruses.
The technique is based on fusing a destabilizing peptide to the protein of interest. This fusion protein is immediately degraded unless the destabilizing peptide is bound by a small synthetic ligand that shields the protein and allows it to exert its normal function. Removal and re-addition of the ligand allow conditional and reversible disruption of the fusion proteins.
By adapting this strategy for viruses the team opens the door for detailed studies of protein function in herpes viruses and other viral families.