Reverse Genetics of Mononegavirales: The Rabies Virus Paradigm

Abstract

The neurotropic rabies virus (RABV) is a prototype member of the Mononegavirales order of viruses and is the most signifi cant human pathogen of the Rhabdoviridae family. A reverse genetics system for RABV was established almost 20 years ago, providing a paradigm for other Mononegavirales members as well. The availability of engineered recombinant viruses opened a new era to study common aspects of Mononegavirales biology and specifi c aspects of the unique lifestyle and pathogenesis of individual members. Above all, the knowledge gained has allowed engineering of benefi cial biomedical tools such as viral vectors, vaccines, and tracers. In this chapter, the development of the classical rabies virus reverse genetics approach is described, and some of the most exciting biomedical applications for recombinant RABV and other Mononegavirales are briefl y addressed. Mononegavirales : A Huge Diversity of Similar VirusesThe order Mononegavirales , or nonsegmented negative strand RNA viruses (NNSV), comprises the families of Rhabdoviridae , Paramyxoviridae , Filoviridae , and Bornaviridae . Members of the Rhabdoviridae family have the broadest host range among the Mononegavirales and infect plants, insects, fi sh, aquatic, aerial, and terrestrial animals, and humans (for reviews, see Fu 2005 ; Pringle 2005 ). Remarkably, the only globally important human pathogen among rhabdoviruses is the rabies virus (RABV) of the genus Lyssavirus , which causes rabies encephalitis, a long-known, most dangerous and feared zoonotic disease. In spite of the availability of potent vaccines for animals and humans and effective postexposure

Reverse genetics of rabies virus: new strategies to attenuate virus virulence for vaccine development

“…While a number of excellent reviews have been written focusing on reverse genetics of negative-strand RNA viruses and the history and development of rabies vaccines (Briggs et al 2013;Conzelmann 2013;Finke and Conzelmann 2005;Hicks et al 2012;Nel 2005;Rupprecht et al 2002;Wu et al 2011), this review mainly summarizes the current strategies using reverse genetics to reduce the virulence and improve the safety of RABV for potential use in rabies vaccine production and the development of multivalent vaccines capable of stimulating host immune responses against other pathogens. Finally, some of the issues concerning the application of reverse genetics in negative-strand RNA viruses that need to be addressed are discussed.…”