Abstract
Human herpes simplex viruses (HSV) 1 and 2 are extremely common human pathogens with overlapping disease spectra. Infections due to HSV-1 and HSV-2 are distinguished in clinical settings using sequence-based “typing” assays. Here we describe a case of HSV mistyping caused by a previously undescribed HSV-1 × HSV-2 recombination event in UL27, the HSV gene that encodes glycoprotein B. This is the first documented case of HSV mistyping caused by an HSV-1 × HSV-2 recombination event and the first description of an HSV interspecies recombination event in UL27, which is frequently used as a target for diagnostics and experimental therapeutics. We also review the primer and probe target sequences for a commonly used HSV typing assay from nearly 700 HSV-1 and HSV-2 samples and find that about 4% of HSV-1 samples have a single nucleotide change in at least one of these loci, which could impact assay performance. Our findings illustrate how knowledge of naturally occurring genomic variation in HSV-1 and HSV-2 is essential for the design and interpretation of molecular diagnostics for these viruses.
Highlights
Human herpes simplex viruses (HSV) 1 and 2 cause chronic, incurable infections in 3 billion and 500 million people, worldwide, respectively [1,2]
For the first time, a case of HSV mistyping resulting from a HSV-1 × HSV-2 recombination event in the HSV-2 UL27 gene, which encodes glycoprotein B
The primer and probe sequences for our HSV typing assay are homologous to sequences within the HSV UL27 gene. We reviewed this gene in an alignment of the HSV-1 strain 17, HSV-2 SD90e, and the CT_Sample9 consensus genomes
Summary
Human herpes simplex viruses (HSV) 1 and 2 cause chronic, incurable infections in 3 billion and 500 million people, worldwide, respectively [1,2]. There is extensive overlap in the spectrum of disease that can be attributed to each virus. The identification of the species of HSV responsible for an infection can provide important diagnostic and prognostic information and is recommended in some clinical contexts by the 2015 Centers for Disease Control and Prevention (CDC) Sexually. Transmitted Diseases (STD) Treatment Guidelines [3] and by current Infectious Diseases Society of America (IDSA) Guidelines [4]. HSV speciation or “typing” is performed using commercial test kits or testing assays developed by clinical laboratories. All fourteen FDA-approved HSV typing assays [5]
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