TY - JOUR
T1 - SARS-CoV-2 spike protein co-opts VEGF-A/neuropilin-1 receptor signaling to induce analgesia
AU - Moutal, Aubin
AU - Martin, Laurent F.
AU - Boinon, Lisa
AU - Gomez, Kimberly
AU - Ran, Dongzhi
AU - Zhou, Yuan
AU - Stratton, Harrison J.
AU - Cai, Song
AU - Luo, Shizhen
AU - Gonzalez, Kerry Beth
AU - Perez-Miller, Samantha
AU - Patwardhan, Amol
AU - Ibrahim, Mohab M.
AU - Khanna, Rajesh
PY - 2021/1/1
Y1 - 2021/1/1
N2 - Global spread of severe acute respiratory syndrome coronavirus 2 continues unabated. Binding of severe acute respiratory syndrome coronavirus 2's spike protein to host angiotensin-converting enzyme 2 triggers viral entry, but other proteins may participate, including the neuropilin-1 receptor (NRP-1). Because both spike protein and vascular endothelial growth factor-A (VEGF-A)-a pronociceptive and angiogenic factor, bind NRP-1, we tested whether spike could block VEGF-A/NRP-1 signaling. VEGF-A-triggered sensory neuron firing was blocked by spike protein and NRP-1 inhibitor EG00229. Pronociceptive behaviors of VEGF-A were similarly blocked through suppression of spontaneous spinal synaptic activity and reduction of electrogenic currents in sensory neurons. Remarkably, preventing VEGF-A/NRP-1 signaling was antiallodynic in a neuropathic pain model. A "silencing" of pain through subversion of VEGF-A/NRP-1 signaling may underlie increased disease transmission in asymptomatic individuals.
AB - Global spread of severe acute respiratory syndrome coronavirus 2 continues unabated. Binding of severe acute respiratory syndrome coronavirus 2's spike protein to host angiotensin-converting enzyme 2 triggers viral entry, but other proteins may participate, including the neuropilin-1 receptor (NRP-1). Because both spike protein and vascular endothelial growth factor-A (VEGF-A)-a pronociceptive and angiogenic factor, bind NRP-1, we tested whether spike could block VEGF-A/NRP-1 signaling. VEGF-A-triggered sensory neuron firing was blocked by spike protein and NRP-1 inhibitor EG00229. Pronociceptive behaviors of VEGF-A were similarly blocked through suppression of spontaneous spinal synaptic activity and reduction of electrogenic currents in sensory neurons. Remarkably, preventing VEGF-A/NRP-1 signaling was antiallodynic in a neuropathic pain model. A "silencing" of pain through subversion of VEGF-A/NRP-1 signaling may underlie increased disease transmission in asymptomatic individuals.
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U2 - 10.1097/j.pain.0000000000002097
DO - 10.1097/j.pain.0000000000002097
M3 - Article
C2 - 33009246
AN - SCOPUS:85098602737
SN - 0304-3959
VL - 162
SP - 243
EP - 252
JO - Pain
JF - Pain
IS - 1
ER -