TY - JOUR
T1 - Neurokinin-1 enables measles virus trans-synaptic spread in neurons
AU - Makhortova, Nina R.
AU - Askovich, Peter
AU - Patterson, Catherine E.
AU - Gechman, Lisa A.
AU - Gerard, Norma P.
AU - Rall, Glenn
PY - 2007/5/25
Y1 - 2007/5/25
N2 - 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.
AB - 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.
KW - CD46
KW - Central nervous system
KW - Fusion
KW - Fusion inhibitory peptide
KW - Measles
KW - Neurokinin-1
KW - Neuron
KW - Spread
KW - Subacute sclerosing panencephalitis
KW - Substance P
UR - http://www.scopus.com/inward/record.url?scp=34247261574&partnerID=8YFLogxK
U2 - 10.1016/j.virol.2007.02.033
DO - 10.1016/j.virol.2007.02.033
M3 - Article
SN - 0042-6822
VL - 362
SP - 235
EP - 244
JO - Virology
JF - Virology
IS - 1
ER -