[Genotyping diagnosis of acyclovir resistant herpes simplex virus]

Abstract

Herpes simplex virus resistant to acyclovir (ACV) is a major concern among immunocompromised patients. ACV resistance might be due to mutations located in one of the two genes involved in ACV mechanism of action, the thymidine kinase gene (TK, involved in 95% of the cases) and the DNA polymerase gene. TK gene mutations consist, in half of the cases, in nucleotide insertion or deletion, occurring most of the time in G or C homopolymers considered as hot spots. Half of the other cases involves nucleotide substitutions leading to amino acids substitutions. Studies of sensitive strains revealed a high degree of TK polymorphism, many mutations being not implied in ACV resistance. At the present time, resistance detection can be performed by phenotypic tests that require virus culture and results cannot be given to the physician before 7 to 10 days. Genotyping diagnosis performed directly from clinical samples would allow to detect resistance more rapidly, in order to switch quickly to an appropriate treatment by foscarnet or cidofovir.