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Virologie. Volume 16, Number 1, 43-57, Janvier-Février 2012, revue

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Author(s) : Pascale Bonnafous, Agnès Gautheret-Dejean, Henri Agut

Summary : The human herpesvirus 6 (HHV-6) is an opportunistic agent like the genetically related human cytomegalovirus (HCMV). After primary infection usually occurring in childhood, it may reactivate during immunosuppression, leading to symptoms of varying severity, such as encephalitis. If no antiviral regimen has been formally approved yet, the anti-HCMV drugs, ganciclovir (GCV), cidofovir (CDV) and foscarnet (PFA), are also active in vitro and in vivo against HHV-6. However, prolonged treatment may lead to the selection of mutants resistant to these drugs. In recent years, resistant clinical or laboratory HHV-6 strains have emerged and have been studied. The involvement of various viral genomic mutations in the resistance has been addressed by different genetic, functional or structural approaches, enabling to understand the underlying molecular mechanisms. Until now, the evidence of the role of a mutation in GCV resistance has only been obtained for the M318V substitution of the viral phosphotransferase, enzyme involved in metabolism of GCV, by means of phenotype restoration tests. This technique remains to be developed to study mutations in the gene of the final target of antiviral drugs, the viral DNA polymerase.

Keywords : HHV-6, antiviral, resistance, DNA polymerase