Andy
Senior Member (Voting rights)
Abstract
Post-translational modifications (PTMs) regulate protein structure, function, and interactions, playing pivotal roles in cellular processes and disease progression. Lactate, a byproduct of the Warburg effect, accumulates excessively during viral infections and functions as a signaling molecule, disrupting mitochondrial antiviral-signaling protein activity and facilitating viral immune evasion. Lactylation, a recently identified PTM derived from lactate metabolism, links cellular metabolism and immune regulation by modulating gene expression and metabolic reprogramming. It also serves as a mechanism for viruses to modulate host immunity. Despite its emerging importance, its role with respect to viruses infecting humans and animals remains poorly understood. Investigating its impact on metabolic, protein modifications, and immune signaling may reveal novel immune evasion strategies and therapeutic targets. This review aims to provide an overview of the fundamental features and regulatory functions of lactylation, explore its association with viral infections, and offer insights into how lactylation influences metabolic and immune responses during virus–host interactions.Author summary
Viruses exploit host cellular machinery for replication, relying on host metabolic pathways to establish a conducive microenvironment for their proliferation. A notable consequence of this metabolic reprogramming is the accumulation of lactate, a glycolytic byproduct. Beyond its well-established role in metabolism, recent studies have identified lactate as a signaling molecule that drives lactylation, a newly discovered post-translational modification, that regulates gene expression, modulates immune responses, and influences cellular functionality. Despite these progresses, the role of lactylation in viral pathogenesis remains poorly characterized. In this review, we systematically examine the impact of lactylation on virus–host interactions, with particular emphasis on how viral pathogens exploit lactate-driven modifications to regulate host immune defenses, disrupt antiviral signaling cascades, and reprogram immune cell functionality. Lactylation modification establishes a critical link between cellular metabolism, epigenetic regulation, and immune modulation in the context of viral infections. By elucidating the mechanistic underpinnings of lactylation, we may reveal novel antiviral strategies and gain crucial insights into its regulatory roles in viral pathogenesis and host immunity.Open access
