Genome-Wide Surveillance of Genital Herpes Simplex Virus Type 1 From Multiple Anatomic Sites Over Time

Abstract

Here we present genomic and in vitro analyses of temporally separated episodes of herpes simplex virus type 1 (HSV-1) shedding by an HSV-1–seropositive and human immunodeficiency virus (HIV)/HSV-2–seronegative individual who has frequent recurrences of genital HSV-1. Using oligonucleotide enrichment, we compared viral genomes from uncultured swab specimens collected on different days and from distinct genital sites. We found that viral genomes from 7 swab specimens and 3 cultured specimens collected over a 4-month period from the same individual were 98.5% identical. We observed a >2-fold difference in the number of minority variants between swab specimens from lesions, swab specimens from nonlesion sites, and cultured specimens. This virus appeared distinct in its phylogenetic relationship to other strains, and it contained novel coding variations in 21 viral proteins. This included a truncation in the UL11 tegument protein, which is involved in viral egress and spread. Normal immune responses were identified, suggesting that unique viral genomic features may contribute to the recurrent genital infection that this participant experiences.

High-throughput sequencing in diagnostics and prevention of herpes simplex virus infection (Herpesviridae, Alphaherpesvirinae, Simplexvirus, Human alphaherpesvirus 1)

“…Она может быть симптоматической или асимптоматической в зависимости от иммунного статуса хозяина и других факторов. значимых маркеров вирулентности в геноме ВПГ необходимы дополнительные исследования генома изолятов вируса, выделенных от пациентов с той или иной формой патологии [30].…”

In vitroevolution of herpes simplex virus 1 (HSV-1) reveals selection for syncytia and other minor variants in Vero cell culture

“…The presence of defective UL13 variants in HSV-1 populations is not unique to the F strain. In a recent publication by our group that compared a cultured clinical isolate to direct-from-patient swab-based sequencing of a genital HSV-1 lesion, we detected UL13 minor variants only in the cultured material [12]. We extended this investigation to two newly isolated clinical genital HSV-1 isolates, and likewise detected UL13-inactivating minor variants in these cultured populations.…”

“…those most frequently observed and/or rapidly selected in newly cultured clinical isolates. Intriguingly, both the UL13 and UL14 variants observed here were also detected in the initial culture passages of the genital HSV-1 isolate v29 [12].…”

“…Minor variants (MVs) within each genome were detected using VarScan 2.4.2 [60], in a similar manner as previously described [11,12,61]. We used parameters intended to eliminate sequencing-induced errors from the initial calling of MVs.…”

“…There have been few studies that have followed a population of HSV-1 through longitudinal sampling of one person [12], or studied known transmission events [11]. These studies imply that viral population diversity can be generally maintained through transmission [11], but that the viral population can drift or adapt during subsequent rounds of latency and reactivation [12]. However, as with most viruses, HSV-1 is quite often studied in cell culture or animal models.…”