(14) Exploring HSV Genomic Variability in Mother-infant Pairs: Towards Understanding Neonatal Transmission Dynamics

Background: Neonatal herpes simplex virus (nHSV) infections present a global health concern, with approximately 14,000 cases reported worldwide each year, including 1,500 cases in the USA alone. These infections often arise from maternal genital shedding of HSV during birth, particularly in the context of the mother’s primary or initial infection. Infected neonates are classified into three different disease categories – central nervous system disease (CNS, 30%), disseminated disease (25%), and skin, eyes, and mouth disease (SEM, 45%). Among these, CNS and disseminated diseases are considered invasive, resulting in 4% or 29% morbidity, respectively. Despite the frequent exposure to HSV during birth, nHSV develops rarely, suggesting the presence of a viral barrier to mother‐to‐infant transmission.

Objectives: Traditionally, the DNA genomes of herpesviruses have been considered stable and therefore not a significant source of variability. This was based on older, low-resolution techniques such as restriction fragment length polymorphisms (RFLP). However, recent advancements in next-generation sequencing (NGS) and bioinformatic tools have revealed previously unseen variability. These variations include minor alleles, dual-strain infections, and recombination events between HSV-1 and HSV-2.

Design/Methods: Recent studies have begun examining HSV genome sequencing data from infant-mother pairs, revealing differing frequencies of HSV variants between pairs. However, these studies are limited by small sample sizes, often based on only one or two cases. Our objective is to expand upon these findings by sequencing a larger number of HSV-1 and HSV-2 infant-mother pairs, allowing for a more comprehensive analysis of HSV sequence variability and its implications for neonatal transmission.

Results: We collected isolates from neonates with nHSV, along with paired maternal samples. Sequencing a subset revealed differences in minor variant frequencies between maternal and neonatal samples, suggesting a potential genomic barrier to HSV transmission. However, further sampling is needed to better understand this putative barrier.

Conclusions: The identification of variability between HSV variants in mothers and their infants is crucial for understanding the existence and nature of the barrier to transmission. This knowledge may inform the development of novel diagnostic tools, therapeutic strategies, and preventive measures aimed at reducing the devastating outcomes caused by nHSV infections.