Chapter 2 - Rabies virus

Abstract

This chapter introduces the rabies virus as the etiologic agent that causes the disease known as rabies. Rabies virus and 15 rabies-like viruses belong to the genus Lyssavirus in the family Rhabdoviridae of the order Mononegavirales that includes all negative-sense, single-stranded RNA viruses. Lyssaviruses have five major polypeptides: the nucleoprotein (N), phosphoprotein (P), and the large virion-associated RNA polymerase (L) that make up the ribonucleoprotein (RNP) core of the virus, the matrix protein (M) that is associated with the lipid-bilayer envelope that surrounds the RNP core, and the glycoprotein (G) that forms the trimeric spikes on the virion surface. The RNP complex of rabies is a stable helical structure of genome RNA tightly encapsidated and protected by N in association with the P and L proteins, the details of which are described. Transcription of the lyssavirus genes to produce individual mRNAs, which are translated to form the viral proteins as well as replication of the genome N-vRNA complexes, and the mechanisms and regulation of genome transcription and replication are described, although not fully understood. The sequence of events in the rabies virus life cycle, its replication in cell culture and in the animal, is divided into three phases. The early (first) phase includes virus attachment to receptors on susceptible host cells, entry and uncoating of the virus particle, and liberation of the helical RNP in the cytoplasm. The middle (second) phase includes transcription and replication of the helical RNP in the cytoplasm, and the late (third) phase includes virus assembly and egress from the infected cell. These three phases of rabies virus replication are described in detail as well as how the virus is transported (spreads) from cell to cell.