Environmental Stress Causes Lethal Neuro-Trauma during Asymptomatic Viral Infections

Cell Host Microbe. 2017 Jul 12;22(1):48-60.e5. doi: 10.1016/j.chom.2017.06.010.

Abstract

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.

Keywords: CO2; Drosophila; VSV; carbon dioxide; glial cell; innate immunity; neuroimmunology; neuron; syncytia; vesicular stomatitis virus.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Anopheles / immunology
  • Anopheles / virology
  • Antiviral Agents / pharmacology
  • Behavior, Animal
  • Carbon Dioxide / pharmacology*
  • Drosophila melanogaster / immunology
  • Drosophila melanogaster / virology
  • Environment*
  • Glycoproteins / metabolism
  • Hydrogen-Ion Concentration
  • Immunity, Innate
  • Neuroglia / immunology
  • Neuroglia / virology
  • Neurons / immunology
  • Neurons / virology*
  • RNA Interference
  • Sindbis Virus / immunology
  • Sindbis Virus / pathogenicity
  • Stress, Physiological*
  • Vesicular stomatitis Indiana virus / drug effects*
  • Vesicular stomatitis Indiana virus / pathogenicity*
  • Viral Plaque Assay
  • Viral Proteins / metabolism
  • Virus Diseases* / immunology
  • Virus Diseases* / virology
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Glycoproteins
  • Viral Proteins
  • Carbon Dioxide