Neurokinin-1 enables measles virus trans-synaptic spread in neurons.
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.
Makhortova
Nina R
NR
Division of Basic Science, The Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
Askovich
Peter
P
Patterson
Catherine E
CE
Gechman
Lisa A
LA
Gerard
Norma P
NP
Rall
Glenn F
GF
D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D008457:Measles / Q000821:virology*; D008459:Measles virus / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D064729:Neurokinin-1 Receptor Antagonists; D009474:Neurons / Q000821:virology*; D018377:Neurotransmitter Agents / Q000378:metabolism; D018040:Receptors, Neurokinin-1 / Q000235:genetics / Q000502:physiology*; D011991:Receptors, Virus / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D016019:Survival Analysis; D014709:Vero Cells; D014760:Viral Fusion Proteins / Q000378:metabolism
D064729:Neurokinin-1 Receptor Antagonists; D018377:Neurotransmitter Agents; D018040:Receptors, Neurokinin-1; D011991:Receptors, Virus; D014760:Viral Fusion Proteins