Neuronal apoptosis pathways in Sindbis virus encephalitis.

In their daily battles against microbial pathogens, infected hosts need to strike a balance between fighting the invaders and minimizing the overall destruc­tion caused by their defensive campaign. Limited and localized responses are crucial to reduce the amount of “collateral damage” that may result in the elimination of vital components of the host essential for the survival of the infected organism. For instance, an excess in prophylactic programmed cell death or an exacerbated cytotoxic T-cell response beyond a certain threshold could cause irreparable harm to fundamental tissues, leading to irreversible sequelae or death. The regulation of the protective response is particularly important in cases like viral infections that cause encephalitis, as most of the target cells belong to non-renewable populations, some of which are essential for life. In the case of Sindbis virus (SV), neurons are the main site of viral replication, and virus-induced neuronal cell death correlates with Sindbis vir­ulence. Specifically, apoptotic mechanisms triggered in infected cells appear to be the main determining factors of the outcome of an infection. In this regard, Sindbis represents a model system to study viruses that induce enceph­alomyelitis affecting humans, in which decisions taken at the cellular level in infected neurons ultimately dictate the fate of the entire organism. To predict the outcome of infections and to devise strategies to treat encephalitis, it is crucial to identify both host- and virus-related factors that modulate cell death and disease. Ultimately, a better understanding of the molecular mechanisms governing neuronal cell fate under conditions of stress will also help us gain insight into several neurological diseases that affect humans.