Herpes simplex virus type 1 isolated from newborns reveals viral diversity between and within patients

Herpes simplex virus (HSV) type 1 and 2 infect over 14,000 newborns each year globally, with most cases (55%) causing a severe outcome that can be fatal if untreated. Neonatal disease severity and long-term outcomes remain unpredictable, and elucidating viral factors that contribute to these outcomes remains a challenge. However, through viral genomic and phenotypic analysis of HSV isolated from neonatal patients, we can begin to connect aspects of viral diversity with clinical patient data.

Here we have applied viral whole genome sequencing to a collection of residual clinical diagnostic samples from ten neonates who had either mild or severe HSV-1 infections. Samples from different body sites or across recurrences allowed for both within- and between-host comparisons. From 30 residual diagnostic samples, we successfully isolated 14 viral cultures. These cultured viruses enabled additional phenotypic analyses, including in vitro growth evaluation in multiple cell types and an in vivo murine model of infection.

These data highlight the diversity found in HSV-1 isolated from neonates. Through comparative genomics approaches, we demonstrate both within- and between-host diversity of these samples. Growth of cultured isolates in cell-based assays and a murine model of infection reveal additional aspects of within- and between-host differences.

Overall, this study presents the first investigation into the viral diversity of neonatal HSV-1, which is now more common in the US than neonatal HSV-2. Through integration of phenotypic, genomic, and clinical data we characterized these neonatal viral samples to begin unraveling the complexity of neonatal HSV-1 infections.