Rabie Virus Research Paper

Viruses have evolved powerful countermeasures to evade host innate immunity which produces immediate, but non-specific, immune response during infection. Among viruses possessing RNA genomes, the order of negative-single-strand viruses (Mononegavirales) encompasses many human and animal pathogens that cause severe disease, including measles virus, mumps virus and rabies virus.

Rabies is an untreatable disease of humans, which has a case-fatality rate of almost 100% in non-vaccinated individuals. The etiological agents of rabies are viruses of the globally distributed Lyssavirus genus, the best characterized of which is rabies virus (RABV), which infects diverse mammalian species, being transmitted to humans most commonly by bites from infected

However, successful achievement of the virus cycle relies on the preservation of the neuronal network. RABV propagation in the NS requires that neuronal cell bodies are not damaged by premature apoptosis and that the integrity of axons and dendrites is preserved, at least during the period of time required for the virus to reach the salivary glands [4]. Indeed, the histopathological changes in the brain are relatively mild, with inflammatory cell infiltration in the leptomeninges, perivascular cuffing and infiltrates of mononuclear cells in the parenchyma. Typical inclusions known as Negri bodies are present in the cytoplasm of infected neurons and correspond to aggregates of viral proteins. Besides neurons, other cell types such as astrocytes are found to be infected [5]. There are also signs of microglia activation resulting in Babes nodules and neuronophagia. This surprising lack of major histopathological changes and neuronal death or apoptosis raised the hypothesis that the clinical outcomes following RABV infection resulted from major neuronal dysfunction, the basis of which remained so far unknown. Further, the contribution of glial cells and their crosstalk with neurons remained

Indeed, RABV seems to minimize the inflammation within the nervous tissue in several different ways [6,7]: (i) in infected pyramidal and Purkinje neurons, TLR3 is sequestered in the Negri body8, hindering subsequent activation of signaling pathways and IFN expression, (ii) P protein competitively binds to IRF-3 and block the translocation and IFN production, (iii) several proteins in NF-kB pathway, including RelA43, are modulated by M protein, (iv) G protein association with MAST2 and PTPN4 enables the infected neuron to evade apoptosis. All features above contribute to the subdued inflammatory response in the brain, hence to the extended survival of neurons up to the point of