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Pathogenesis of rabies.

B Dietzschold1, M Schnell, H Koprowski

  • 1Department of Microbiology, Center for Neurovirology, Thomas Jefferson University, Philadelphia, PA, USA. Bernhard.dietzschold@jefferson.edu

Current Topics in Microbiology and Immunology
|June 29, 2005
PubMed
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Rabies virus (RV) causes fatal central nervous system disease by infecting neurons and inhibiting essential protein synthesis. Viral proteins like G and P play roles in neuroinvasion and pathogenesis, contributing to lethal outcomes.

Area of Science:

  • Neuroscience
  • Virology
  • Molecular Biology

Background:

  • Rabies is a fatal neurological disease caused by the rabies virus (RV), a negative-stranded RNA virus.
  • RV pathogenesis is complex, involving viral genetic factors and host-pathogen interactions within the central nervous system (CNS).
  • Neuroinvasiveness, particularly transsynaptic neuronal spread, is a hallmark of RV infection.

Purpose of the Study:

  • To elucidate the viral factors and mechanisms contributing to rabies virus pathogenesis and neuroinvasiveness.
  • To understand the role of specific RV proteins, such as G and P, in viral spread and disease outcome.
  • To identify the key molecular events leading to the lethal neurological dysfunction observed in rabies.

Main Methods:

  • Analysis of RV genetic elements, including the G and L genes, in relation to pathogenesis.

Related Experiment Videos

  • Investigation of viral protein functions, specifically the G protein in transsynaptic spread and the P protein in axonal transport.
  • Examination of molecular mechanisms underlying neuronal dysfunction during RV infection.

    • Main Results:

    • Viral elements regulating gene expression, particularly the L gene, are implicated in RV pathogenesis.
    • The RV G protein mediates the spread of the virus from post-synaptic to pre-synaptic sites.
    • The RV P protein may be crucial for retrograde axonal transport within neurons.
    • Inhibition of protein synthesis essential for neuronal function is a primary cause of lethal neurological disease.

    Conclusions:

    • RV pathogenesis is a multigenic trait influenced by viral proteins like G and P.
    • Understanding RV neuroinvasion and mechanisms of neuronal dysfunction is critical for combating rabies.
    • Targeting viral factors involved in gene expression, neuronal spread, and protein synthesis inhibition may offer therapeutic strategies.