Recognition of single-stranded RNA viruses by Toll-like receptor 7

TLDR

Viral infections trigger innate immunity, and Toll‑like receptors recognize pathogen nucleic acids, with viral genomes providing distinct signatures such as high CpG content and double‑stranded RNA. Recognition of single‑stranded RNA viruses by TLR7 depends on intact endocytic pathways. TLR7 detects single‑stranded RNA viruses such as vesicular stomatitis and influenza, activating plasmacytoid dendritic cells and B cells to express costimulatory molecules and cytokines, and mice lacking TLR7 or MyD88 show diminished responses to infection, confirming TLR7’s role in viral recognition.

Abstract

Viral infection of mammalian host results in the activation of innate immune responses. Toll-like receptors (TLRs) have been shown to mediate the recognition of many types of pathogens, including viruses. The genomes of viruses possess unique characteristics that are not found in mammalian genomes, such as high CpG content and double-stranded RNA. These genomic nucleic acids serve as molecular signatures associated with viral infections. Here we show that TLR7 recognizes the single-stranded RNA viruses, vesicular stomatitis virus and influenza virus. The recognition of these viruses by plasmacytoid dendritic cells and B cells through TLR7 results in their activation of costimulatory molecules and production of cytokines. Moreover, this recognition required intact endocytic pathways. Mice deficient in either the TLR7 or the TLR adaptor protein MyD88 demonstrated reduced responses to in vivo infection with vesicular stomatitis virus. These results demonstrate microbial ligand recognition by TLR7 and provide insights into the pathways used by the innate immune cells in the recognition of viral pathogens.