Impaired learning resulting from Respiratory Syncytial Virus infection

Janyra A. Espinoza, Karen Bohmwald, Pablo F. Céspedes, Roberto S. Gómez, Sebastián A. Riquelme, Claudia M. Cortés, Javier A. Valenzuela, Rodrigo A. Sandoval, Floria C. Pancetti, Susan M. Bueno, Claudia A. Riedel, and Alexis M. Kalergis
PNAS first published May 6, 2013 https://doi.org/10.1073/pnas.1217508110

  1. Edited by Peter Palese, Mount Sinai School of Medicine, New York, NY, and approved April 15, 2013 (received for review October 15, 2012)

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.

Footnotes

  • ↵1To whom correspondence may be addressed. E-mail: akalergis{at}bio.puc.cl or claudia.riedel{at}unab.cl.

  • Author contributions: S.M.B., C.A.R., and A.M.K. designed research; J.A.E., K.B., P.F.C., R.S.G., C.M.C., and J.A.V. performed research; S.A.R., R.A.S., and F.C.P. analyzed data; and J.A.E., S.M.B., C.A.R., and A.M.K. wrote the paper.

  • The authors declare no conflict of interest.

  • This article is a PNAS Direct Submission.

  • This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1217508110/-/DCSupplemental.

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RSV infection in the CNS
Janyra A. Espinoza, Karen Bohmwald, Pablo F. Céspedes, Roberto S. Gómez, Sebastián A. Riquelme, Claudia M. Cortés, Javier A. Valenzuela, Rodrigo A. Sandoval, Floria C. Pancetti, Susan M. Bueno, Claudia A. Riedel, Alexis M. Kalergis
Proceedings of the National Academy of Sciences May 2013, 201217508; DOI: 10.1073/pnas.1217508110
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