HSV-1 metabolic hijacking: Mechanisms to precision therapeutics

Abstract

ABSTRACT Herpes Simplex Virus Type 1 (HSV-1) strategically reprograms host cell metabolism to fulfill its replicative needs and establish persistent infection. This hijacking extends across glucose, lipid, amino acid, and nucleotide pathways, diverting resources toward viral biosynthesis. Critically, the resulting metabolic landscape is not neutral but actively immunosuppressive. By altering the availability of key metabolites and cellular energy states, HSV-1 impairs the function of innate and adaptive immune cells, including antigen presentation by dendritic cells and the effector response of T cells, thereby enabling immune evasion. This review highlights that a systematic understanding of HSV-1-induced immunometabolic dysregulation reveals novel therapeutic targets. Exploiting these metabolic vulnerabilities – through pharmacological intervention or engineered oncolytic viruses – offers a promising precision medicine approach against HSV-1 infection and related pathologies.