Chapter 12 : Susceptibility Test Methods: Viruses

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This chapter discusses the clinical situations in which antiviral resistance has emerged, thus necessitating in vitro susceptibility testing, and provides an overview of the phenotypic and genotypic susceptibility testing methods that have been employed to detect resistance. Phenotypic assays are better suited to assess the combined effect of multiple resistance mutations on drug susceptibility. This is especially important for viruses such as hepatitis B virus (HBV), human cytomegalovirus (HCMV), and human immunodeficiency virus type 1 (HIV-1), which acquire resistance-associated mutations in multiple genes that may manifest as new patterns of resistance, cross-resistance, multidrug resistance, or even reversal of resistance. As clinical strains of HCMV and varicella-zoster virus (VZV) are cell-associated and because low-titer cell-free stocks are less stable during storage, infected cell suspensions (obtained by trypsin treatment of the infected monolayer) can be conveniently used for these viruses. Advantages of antiviral susceptibility testing by flow cytometry include the potential for automation, the objectivity of the assay, and a shorter turnaround time relative to the plaque-reduction assay (PRA). PCR amplification followed by restriction digestion could recognize mutant virus when present at 10% of the total virus population. The major advantage of this PCR-restriction endonuclease method is the speed with which UL97 mutations can be identified, since HCMV sequences can be directly amplified from many clinical samples. Genotypic assays do allow more rapid and efficient detection of resistance than phenotypic assays and may allow earlier detection of emerging resistance than phenotypic assays.

Citation: Arens M, Swierkosz E. 2009. Susceptibility Test Methods: Viruses, p 134-149. In Specter S, Hodinka R, Young S, Wiedbrauk D (ed), Clinical Virology Manual, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815974.ch12
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Proposed guidelines for antiviral susceptibility results of herpes group and influenza viruses

Citation: Arens M, Swierkosz E. 2009. Susceptibility Test Methods: Viruses, p 134-149. In Specter S, Hodinka R, Young S, Wiedbrauk D (ed), Clinical Virology Manual, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815974.ch12

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