Transolfactory neuroinvasion by viruses threatens the human brain

Acta Virol. 2015 Dec;59(4):338-49. doi: 10.4149/av_2015_04_338.


Viral neuroinvasion via the olfactory system has been investigated in a variety of virus-animal models by scientists in many fields including virologists, pathologists, and neurologists. In humans, herpes simplex virus type 1 (HSV-1), human herpesvirus 6 (HHV-6), Borna disease virus, rabies virus, and influenza A virus have been shown to take the olfactory route for neuroinvasion based on forensic and post-mortem specimens. This article briefly summarizes the anatomy, physiology, and immunology of the olfactory system and presents a battery of neurovirulent viruses that may threaten the human brain by invading through this peripheral pathway, especially focusing on two of the most intensively studied viruses--HSV-1 and influenza A virus. Viruses may insidiously invade the olfactory neural network not only to precipitate encephalitis/encephalopathy but also to promote the development of neurodegenerative and demyelinating disorders. Substantial information obtained by analyzing human specimens is required to argue for or against this hypothesis.

Keywords: virus; olfactory neuron; human brain; encephalitis; neurodegenerative disorders..

Publication types

  • Review

MeSH terms

  • Animals
  • Brain / immunology
  • Brain / virology*
  • Humans
  • Olfactory Mucosa / immunology
  • Olfactory Mucosa / virology*
  • Virus Diseases / immunology
  • Virus Diseases / virology*
  • Virus Physiological Phenomena*