Toll-like receptor 4 – a multifunctional virus recognition receptor

TLR4 is a single-pass transmembrane protein whose structure and function as a pattern recognition receptor (PRR) are highly conserved in mammals.TLR4 can be located on the cell surface and/or within cytoplasmic vesicles.TLR4 participates in direct and indirect interactions with viruses and viral proteins to trigger antiviral responses.In several instances, TLR4 polymorphisms can influence virulence.TLR4 agonists are being used to improve vaccine efficacy.Extracellular proteins, including antimicrobial peptides and danger-associated molecular patterns (DAMPs) impact TLR-mediated antiviral responses. Since the initial description of Toll receptors in Drosophila and their mammalian counterparts Toll-like receptors (TLRs), numerous fundamental and applied studies have explored their crucial role as sensors of pathogen-associated molecular patterns (PAMPs). Among the ten human TLRs, TLR4 is particularly well known for its ability to detect lipopolysaccharides (LPS), a component of the Gram-negative bacterial cell wall. In addition to its archetypal functions, TLR4 is also a versatile virus sensor. This review provides a background on the discovery of TLR4 and how this knowledge laid a foundation for characterization of its diverse roles in antiviral responses, examined through genetic, biochemical, structural, and immunological approaches. These advances have led to a deeper understanding of the molecular functions that enable TLR4 to orchestrate multi-nodal control by professional antigen-presenting cells (APCs) to initiate appropriate and regulated antiviral immune responses. Since the initial description of Toll receptors in Drosophila and their mammalian counterparts Toll-like receptors (TLRs), numerous fundamental and applied studies have explored their crucial role as sensors of pathogen-associated molecular patterns (PAMPs). Among the ten human TLRs, TLR4 is particularly well known for its ability to detect lipopolysaccharides (LPS), a component of the Gram-negative bacterial cell wall. In addition to its archetypal functions, TLR4 is also a versatile virus sensor. This review provides a background on the discovery of TLR4 and how this knowledge laid a foundation for characterization of its diverse roles in antiviral responses, examined through genetic, biochemical, structural, and immunological approaches. These advances have led to a deeper understanding of the molecular functions that enable TLR4 to orchestrate multi-nodal control by professional anti