Testing the susceptibility of human herpesviruses to antivirals

Herpesviruses cause chronic lifelong infections in humans and may cause life-threatening diseases in immunosuppressed patients. Antiviral drugs targeted to viral DNA polymerase, such as acyclovir, penciclovir, ganciclovir, foscarnet and cidofovir, are currently available and have been proven to be efficient against clinical symptoms of herpesvirus infections. The resistance of herpesviruses to these drugs is associated with specific mutations of viral genes encoding either DNA polymerase or enzymes phosphorylating nucleoside analogs. Resistance is detected and characterized by means of specific susceptibility assays, which can be classified as phenotypic, genetic and functional. These tests are used both to investigate novel antiviral compounds and look for the emergence of resistant viruses in treated patients in case of clinical failure. Although susceptibility assays are often time consuming and present some limitations regarding the interpretation of their results, their use in the monitoring of antiherpetic treatments should be promoted and improved, in parallel to the development of novel efficient drugs.