Mechanisms of Street Rabies Strains' Host Mortality: A Review

Rabies is an almost ۱۰۰% lethal zoonotic encephalitis induced by the rabies virus (RABV) upon its infiltration of the central nervous system (CNS). Street rabies virus (SRV) strains exhibit pronounced neuroinvasiveness, immune evasion, and restricted neuronal apoptosis, thereby promoting extended intraneuronal replication. Instead of causing widespread neuronal death, SRV causes metabolic, synaptic, and electrophysiological dysfunction in infected neurons by blocking interferon pathways, reducing the synthesis of antiviral cytokines, and delaying apoptosis. Neuropathological traits include microglial activation, neuronophagy, and moderate inflammation facilitated by MAPK and NF-κB signaling pathways. The virus strain, dose, inoculation route, and host genetics all affect how deadly the disease is. Fas ligand–mediated T-cell apoptosis and the integrity of the blood–brain barrier facilitate the virus's persistence in the body. Environmental factors, such as increased ambient temperature, can affect the course of diseases) Fig.۱). Molecular insights indicate that transferrin receptor ۱ is involved in viral entry and highlight the roles of autophagy, apoptosis, and cytoskeletal remodeling in pathogenesis. These mechanisms clarify SRV's unique lethality and uncover novel targets for therapeutic and vaccine strategies aimed at diminishing rabies morbidity and mortality.

کلیدواژه ها:

rabies ، apoptosis ، inflammation ، cytokines ، neurological