Neurokinin-1 enables measles virus trans-synaptic spread in neurons

Nina R. Makhortova, Peter Askovich, Catherine E. Patterson, Lisa A. Gechman, Norma P. Gerard, Glenn Rall

Research output: Contribution to journalArticlepeer-review

82 Scopus citations

Abstract

Measles virus (MV), a morbillivirus that remains a significant human pathogen, can infect the central nervous system, resulting in rare but often fatal diseases, such as subacute sclerosing panencephalitis. Previous work demonstrated that MV was transmitted trans-synaptically and that, while a cellular receptor for the hemagglutinin (H) protein was required for MV entry, it was dispensable for subsequent cell-to-cell spread. Here, we explored what role the other envelope protein, fusion (F), played in trans-synaptic transport. We made the following observations: (1) MV-F expression in infected neurons was similar to that seen in infected fibroblasts; (2) fusion inhibitory peptide (FIP), an inhibitor of MV fusion, prevented both infection and spread in primary neurons; (3) Substance P, a neurotransmitter with the same active site as FIP, also blocked neuronal MV spread; and (4) both genetic deletion and pharmacological inhibition of the Substance P receptor, neurokinin-1 (NK-1), reduced infection of susceptible mice. Together, these data implicate a role for NK-1 in MV CNS infection and spread, perhaps serving as an MV-F receptor or co-receptor on neurons.

Original languageEnglish
Pages (from-to)235-244
Number of pages10
JournalVirology
Volume362
Issue number1
DOIs
StatePublished - May 25 2007

Keywords

  • CD46
  • Central nervous system
  • Fusion
  • Fusion inhibitory peptide
  • Measles
  • Neurokinin-1
  • Neuron
  • Spread
  • Subacute sclerosing panencephalitis
  • Substance P

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