Rhabdoviridae, Rabies Virus

Abstract

Rabies virus (RABV), a member of the Lyssavirus genus belonging to the Rhabdoviridae family in the order Mononegavirales, causes a lethal neurological disease (called rabies) in humans and animals. Although rabies is a vaccine-preventable disease, RABV kills nearly 60,000 people worldwide every year. A bullet-shaped RABV particle encloses a nonsegmented negative strand RNA genome composed of five tandemly arrayed genes encoding structural proteins. RABV is transmitted to humans mainly with saliva of rabid dogs through their bites. After replication in local muscle tissue, RABV enters motor neurons at neuromuscular junctions by receptor-mediated, clathrin-dependent endocytosis and moves to cell bodies using the microtubule-dependent retrograde axonal transport system. Transsynaptic transmission of RABV between neurons leads to RABV invasion of the central nervous system. In the cytoplasm of host cells, RABV produces monocistronic viral mRNAs with a 5′-cap structure and 3′-poly(A) tail and progeny genomes by unique mechanisms mediated by a multifunctional RNA-dependent RNA polymerase. RABV has established strategies to subvert host immune systems, which include antagonistic activities of viral proteins against interferon signaling at different steps. This chapter summarizes our current understanding of the basic biology of RABV and host-virus interactions during infection.