Open AccessEvaluation of Genotypic Antiviral Resistance Testing as an Alternative to Phenotypic Testing in a Patient with DOCK8 Deficiency and Severe HSV-1 Disease
Author(s) -
Amanda M. Casto,
Sean Stout,
Rangaraj Selvarangan,
Alexandra F. Freeman,
Brandon Newell,
Erin D. Stahl,
Atif Ahmed,
Alexander L. Greninger,
Dwight E Yin
Publication year - 2020
Publication title -
the journal of infectious diseases (online. university of chicago press)/the journal of infectious diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.69
H-Index - 252
eISSN - 1537-6613
pISSN - 0022-1899
DOI - 10.1093/infdis/jiaa020
Subject(s) - herpes simplex virus , genotype , biology , disease , phenotype , immunology , virology , hsl and hsv , virus , medicine , genetics , gene , pathology
Antiviral resistance frequently complicates the treatment of herpes simplex virus (HSV) infections in immunocompromised patients. Here we present 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. Finally, we document a likely case of transmitted resistance in HSV-1 between the patient and his brother, who also has DOCK8 deficiency. This event demonstrates that resistant HSV-1 is transmissible among immunocompromised persons.