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Phenotypic and Genotypic Antiviral Resistance Testing of HSV-1 Causing Recurrent Cutaneous Lesions in a Patient with DOCK8 Deficiency

Amanda M. CastoiD, Sean Stout, Rangaraj SelvaranganiD, Alexandra F. FreemaniD, Brandon D. NewelliD, Erin Durrie Stahl, Alexander L. GreningeriD, Dwight Edward YiniD

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Abstract

Antiviral resistance frequently complicates treatment of herpes simplex virus (HSV) infections in immunocompromised patients. Here we review the case of an adolescent boy with dedicator of cytokinesis 8 (DOCK8) deficiency, who experienced recurrent infections with resistant HSV-1. We used both phenotypic and genotypic methodologies to characterize the resistance profile of HSV-1 in the patient and conclude that genotypic testing outperformed phenotypic testing. We also present the first analysis of intrahost HSV-1 evolution in an immunocompromised patient. While HSV-1 can remain static in an immunocompetent individual for decades, the virus from this patient rapidly acquired genetic changes throughout its genome.

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