Rabies is the cause of one of the oldest and most feared diseases of humans and animals- it was recognized in Egypt before 2300 BC and in ancient Greece, where it was welldescribed by Aristotle. Perhaps the most lethal of all infectious diseases, rabies also hasthe distinction of having stimulated one of the great early discoveries in biomedicalscience. In 1885, before the nature of viruses was comprehended, Louis Pasteurdeveloped, tested, and applied a rabies vaccine, thereby opening the modern era ofinfectious disease prevention by vaccination.
Rabies virus is one of the Rhabdoviridae, which encompass over 175 viruses ofvertebrates, invertebrates and plants.
Based on virion properties and serologic relationships four genera containing animalviruses have been recognized in the family Rhabdoviridae.
The rabies virus belongs to the genus Lyssavirus, together with the Mokola virus, Lagosbat virus and Duvenhage virus from Africa and European bat viruses 1 and 2 andAustralian bat lyssavirus. Each of these viruses is considered capable of causing rabieslikedisease in animals and humans. All lyssaviruses use bats as reservoir hosts.
Rhabdovirus virions consist of an outer envelope with large peplomers and an inner,helically coiled cylindrical nucleocapsid. The precise cylindrical form of the nucleocapsidgives the viruses their distinctive bullet or conical shape. The genome is a singlemolecule of linear, negative-sense, single-stranded RNA, 11 to 15 kb in size. The genomeencodes 5 genes in the order 3’-N-NS-M-G-L-5’. The viruses generally have 5 proteins.The glycoprotein that makes up the peplomers contains neutralizing epitopes which aretargets of vaccine-induced immunity as well as epitopes involved in cell-mediatedimmunity. Virions also contain lipids, their composition reflecting the composition of hostcell membranes, and carbohydrate side-chains on the glycoprotein. Rhabdoviruses maybe stable in the environment especially at alkaline pH but are thermolabile and sensitiveto the UV irradiation of sunlight. In clinical practice, rabies virus is easily inactivated bydetergent-based disinfectants.
Viral entry into host cells occurs via fusion of the viral envelope with the cell membrane;all replication steps occur in the cytoplasm.
Virions are formed by the budding of nucleocapsids through cell membranes. Rabies virusbudding takes place mostly upon intracytoplasmic membranes of infected neurons, butalmost exclusively upon plasma membranes of salivary gland epithelial cells. Thereplication of rabies viruses is slow and usually non-cytopathic because it does not shut down host cell protein and nucleic acid synthesis. Rabies virus produces prominentcytoplasmic inclusion bodies (Negri bodies) in infected cells.
Laboratory-adapted (“fixed”) rabies virus replicates well in Vero (African green monkeykidney) cells and BHK-21 (baby hamster kidney) cells, which are the most commonsubstrates for growing animal rabies viruses for vaccine production. Rabies virus alsoreplicates to high titre in suckling mouse and suckling hamster brain.