Replication strategies of rabies virus.
Rabies virus (RV) is a prototype neurotropic virus that causes fatal disease in human and animals. RV infects hosts at the periphery, enters motoneurons or sensory nerves and moves to the central nervous system (CNS) via retrograde axonal transport. At later stages, there is also centrifugal spread to major exit portals, such as the salivary glands. Transmission to other hosts is facilitated by behavioral changes related to the CNS infection. Successful accomplishment of the RV infectious cycle depends on multiple functions of the virus, and of individual virus proteins, all together defining the typical pathogenicity and virulence, i.e. the biological fitness of this virus. In particular, it appears important for RV to sneak into the host without causing pronounced host responses and to preserve, at least for some time, the integrity of infected cells and of the neuronal network. The availability of reverse genetics systems that allow generation of engineered recombinant RV has provided tools for a more detailed analysis of viral functions relevant to the typical RV pathogenesis. Novel developments such as tracking of live fluorescent RV are further increasing the opportunities to decipher RV pathogenicity factors. In this review, we describe different aspects of the molecular biology of RV that are relevant to pathogenesis, with a particular emphasis on the accurate control of RV transcription, gene expression, and replication. In addition, the role of individual virus proteins in maintaining host cell integrity and supporting retrograde transport is discussed. The potential of recombinant RVs with single or multiple pathogenicity factors eliminated is being discussed in terms of vaccine and virus vector development.
Finke
Stefan
S
Max von Pettenkofer-Institute & Gene Center, Ludwig-Maximilians-Universität, München, Feodor-Lynen-Str. 25, 81377 Munich, Germany. finke@lmb.uni-muenchen.de
Conzelmann
Karl-Klaus
KK
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis; D001370:Axonal Transport; D002460:Cell Line; D015967:Gene Expression Regulation, Viral; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000821:virology; D011820:Rabies virus / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology; D014779:Virus Replication