title: Fatal neurological respiratory insufficiency is common among viral encephalitides.
abstract: BACKGROUND
  Neurological respiratory insufficiency strongly correlates with mortality among rodents infected with West Nile virus (WNV), which suggests that this is a primary mechanism of death in rodents and possibly fatal West Nile neurological disease in human patients.
  
  
  METHODS
  To explore the possibility that neurological respiratory insufficiency is a broad mechanism of death in cases of viral encephalitis, plethysmography was evaluated in mice infected with 3 flaviviruses and 2 alphaviruses. Pathology was investigated by challenging the diaphragm, using electromyography with hypercapnia and optogenetic photoactivation.
  
  
  RESULTS
  Among infections due to all but 1 alphavirus, death was strongly associated with a suppressed minute volume. Virally infected mice with a very low minute volume did not neurologically respond to hypercapnia or optogenetic photoactivation of the C4 cervical cord. Neurons with the orexin 1 receptor protein in the ventral C3-5 cervical cord were statistically diminished in WNV-infected mice with a low minute volume as compared to WNV-infected or sham-infected mice without respiratory insufficiency. Also, WNV-infected cells were adjacent to neurons with respiratory functions in the medulla.
  
  
  CONCLUSIONS
  Detection of a common neurological mechanism of death among viral encephalitides creates opportunities to create broad-spectrum therapies that target relevant neurological cells in patients with types of viral encephalitis that have not been treatable in the past.
authors: Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT 84322-4700, USA.
authors: Hong
authors: H
authors: Wang
authors: Venkatraman
authors: V
authors: Siddharthan
authors: Kyle K
authors: KK
authors: Kesler
authors: Jeffery O
authors: JO
authors: Hall
authors: Neil E
authors: NE
authors: Motter
authors: Justin G
authors: JG
authors: Julander
authors: John D
authors: JD
authors: Morrey
mesh_terms: D018354:Alphavirus Infections / Q000473:pathology* / Q000821:virology*; D000818:Animals; D003964:Diaphragm / Q000502:physiology; D004195:Disease Models, Animal; D004576:Electromyography; D018792:Encephalitis, Viral / Q000150:complications*; D005260:Female; D018177:Flavivirus Infections / Q000473:pathology* / Q000821:virology*; D006935:Hypercapnia; D051379:Mice; D010991:Plethysmography; D012131:Respiratory Insufficiency / Q000453:epidemiology* / Q000401:mortality*
keywords: West Nile virus; alphavirus; electromyography; encephalitis; flavivirus; neurons; optogenetic; respiratory
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