A short in vitro-synthesized 5′pppRNA derived from the 5′ and 3′ UTRs of the VSV genome activated the RIG-I signaling pathway and triggered a robust antiviral response that interfered with infection by several pathogenic viruses, including Dengue, HCV, H1N1 Influenza A/PR/8/34 and HIV-1. This evidence concerns the gene RIGI and infection.