Environmental Stress Causes Lethal Neuro-Trauma during Asymptomatic Viral Infections

Asymptomatic infections often proceed undetected, yet can still prime the host to be sensitive to secondary environmental stress. While the mechanisms underlying disease caused by asymptomatic infections are unknown, it is believed that productive pathogen replication is required. We report that the environmental stress of carbon dioxide (CO₂) anesthesia converts an asymptomatic rhabdovirus infection in Drosophila to one that is lethal. This lethality results from a pool of infectious virus in glial cells and is regulated by the antiviral RNAi pathway of the host. CO₂ sensitivity is caused by the fusogenic activity of the viral glycoprotein, which results in fusion of neurons and glia. Expression of the viral glycoprotein, but not a fusion defective mutant, is sufficient to cause CO₂ sensitivity, which can occur even in the absence of productive viral replication. These findings highlight how viral proteins, independent of pathogen replication, may predispose hosts to life-threatening environmental stress.