The immunogenetic basis of severe herpes simplex infections in neonates and children: a review.
Document Type
Article
Publication Date
3-2025
Identifier
DOI: 10.1038/s41390-025-03830-7
Abstract
Human herpes simplex virus (HSV) is a double stranded DNA virus with two distinct types, HSV-1 and HSV-2. The global burden of HSV is high with an estimated 2/3 of the adult population seropositive for at least one of these types of HSV. HSV rarely causes life-threatening disease in immunocompetent children and adults. However, in neonates and children with a developmentally immature immune system it can cause disseminated disease and herpes simplex encephalitis (HSE). Recent studies in children and neonates suggest that genetic risk-factors can contribute to severe HSV phenotypes in neonates and children. In particular, genetic defects in the Toll Like Receptor 3 (TLR3) signaling pathway that attenuate the type I interferon response to HSV are being increasingly recognized in children with severe phenotypes of HSV. In this review, we discuss the epidemiology and immunological aspects of HSV disease in neonates and children and provide an in-depth review of the studies characterizing the role of inborn errors in the TLR3 pathway and other immune genes in HSV. We highlight the need for future research to identify the immunogenetic basis of severe or recurrent HSV disease in neonates and children. IMPACT: Review the epidemiology and phenotypes of herpes simplex virus (HSV) infection in neonates and children. Discuss the mechanisms of immunity against HSV highlighting the developmental vulnerability of neonates and infants to severe HSV disease. Explore in depth the genes and immune pathways that underlie genetic predisposition to severe HSV disease in neonates and children, and outline strategies for multi-disciplinary clinical evaluation of severe disease.
Journal Title
Pediatric research
Volume
97
Issue
4
First Page
1370
Last Page
1380
MeSH Keywords
Humans; Infant, Newborn; Child; Herpes Simplex; Toll-Like Receptor 3; Genetic Predisposition to Disease; Signal Transduction; Phenotype; Immunogenetics; Infant; Herpesvirus 1, Human; Risk Factors
PubMed ID
39827257
Keywords
Herpes Simplex; Toll-Like Receptor 3; Genetic Predisposition to Disease; Signal Transduction; Phenotype; Immunogenetics; Human Herpesvirus 1; Risk Factors
Recommended Citation
Tucker MH, Kalamvoki M, Tilak K, Raje N, Sampath V. The immunogenetic basis of severe herpes simplex infections in neonates and children: a review. Pediatr Res. 2025;97(4):1370-1380. doi:10.1038/s41390-025-03830-7
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