Impaired learning resulting from respiratory syncytial virus infection

Proc Natl Acad Sci U S A. 2013 May 28;110(22):9112-7. doi: 10.1073/pnas.1217508110. Epub 2013 May 6.

Abstract

Respiratory syncytial virus (RSV) is the major cause of respiratory illness in infants worldwide. Neurologic alterations, such as seizures and ataxia, have been associated with RSV infection. We demonstrate the presence of RSV proteins and RNA in zones of the brain--such as the hippocampus, ventromedial hypothalamic nucleus, and brainstem--of infected mice. One month after disease resolution, rodents showed behavioral and cognitive impairment in marble burying (MB) and Morris water maze (MWM) tests. Our data indicate that the learning impairment caused by RSV is a result of a deficient induction of long-term potentiation in the hippocampus of infected animals. In addition, immunization with recombinant bacillus Calmette-Guérin (BCG) expressing RSV nucleoprotein prevented behavioral disorders, corroborating the specific effect of RSV infection over the central nervous system. Our findings provide evidence that RSV can spread from the airways to the central nervous system and cause functional alterations to the brain, both of which can be prevented by proper immunization against RSV.

Keywords: LTD; LTP; behavior; cognition; inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism*
  • Brain / pathology
  • Learning Disabilities / etiology*
  • Learning Disabilities / prevention & control
  • Learning Disabilities / virology
  • Long-Term Potentiation / physiology
  • Maze Learning / physiology
  • Mice
  • Mice, Inbred BALB C
  • Mycobacterium bovis / immunology
  • RNA, Viral / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Respiratory Syncytial Virus Infections / complications*
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / metabolism
  • T-Lymphocytes / immunology
  • Viral Proteins / metabolism*
  • Viral Vaccines / immunology

Substances

  • RNA, Viral
  • Viral Proteins
  • Viral Vaccines