This study investigates the recognition of single-stranded RNA (ssRNA) viruses by Toll-like receptor 7 (TLR7) in plasmacytoid dendritic cells (pDCs) and B cells. The authors demonstrate that TLR7 is essential for the recognition of ssRNA viruses, such as vesicular stomatitis virus (VSV) and influenza virus, by pDCs and B cells. This recognition leads to the activation of costimulatory molecules and the production of cytokines, including type I interferons (IFNs). The study also shows that this recognition requires intact endocytic pathways and the adaptor protein MyD88. Mice deficient in TLR7 or MyD88 exhibit reduced responses to VSV infection. These findings provide insights into the pathways used by innate immune cells to recognize viral pathogens and highlight the importance of TLR7 in the innate antiviral response.This study investigates the recognition of single-stranded RNA (ssRNA) viruses by Toll-like receptor 7 (TLR7) in plasmacytoid dendritic cells (pDCs) and B cells. The authors demonstrate that TLR7 is essential for the recognition of ssRNA viruses, such as vesicular stomatitis virus (VSV) and influenza virus, by pDCs and B cells. This recognition leads to the activation of costimulatory molecules and the production of cytokines, including type I interferons (IFNs). The study also shows that this recognition requires intact endocytic pathways and the adaptor protein MyD88. Mice deficient in TLR7 or MyD88 exhibit reduced responses to VSV infection. These findings provide insights into the pathways used by innate immune cells to recognize viral pathogens and highlight the importance of TLR7 in the innate antiviral response.