Chikungunya Virus and Its Envelope Protein E2 Induce Hyperalgesia in Mice: Inhibition by Anti-E2 Monoclonal Antibodies and by Targeting TRPV1

Carina Z. Segato-Vendrameto, Camila Zanluca, Amanda Z. Zucoloto, Tiago H. Zaninelli, Mariana M. Bertozzi, Telma Saraiva-Santos, Camila R. Ferraz, Larissa Staurengo-Ferrari, Stephanie Badaro-Garcia, Marília F. Manchope, Amanda M. Dionisio, Felipe A. Pinho-Ribeiro, Sergio M. Borghi, Ana Luiza Pamplona Mosimann, Rubia Casagrande, Juliano Bordignon, Victor Fattori, Claudia N.Duarte dos Santos, Waldiceu A. Verri

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Chikungunya virus is an arthropod-borne infectious agent that causes Chikungunya fever disease. About 90% of the infected patients experience intense polyarthralgia, affecting mainly the extremities but also the large joints such as the knees. Chronic disease symptoms persist for months, even after clearance of the virus from the blood. Envelope proteins stimulate the immune response against the Chikungunya virus, becoming an important therapeutic target. We inactivated the Chikungunya virus (iCHIKV) and produced recombinant E2 (rE2) protein and three different types of anti-rE2 monoclonal antibodies. Using these tools, we observed that iCHIKV and rE2 protein induced mechanical hyperalgesia (electronic aesthesiometer test) and thermal hyperalgesia (Hargreaves test) in mice. These behavioral results were accompanied by the activation of dorsal root ganglia (DRG) neurons in mice, as observed by calcium influx. Treatment with three different types of anti-rE2 monoclonal antibodies and absence or blockade (AMG-9810 treatment) of transient receptor potential vanilloid 1 (TRPV1) channel diminished mechanical and thermal hyperalgesia in mice. iCHIKV and rE2 activated TRPV1+ mouse DRG neurons in vitro, demonstrating their ability to activate nociceptor sensory neurons directly. Therefore, our mouse data demonstrate that targeting E2 CHIKV protein with monoclonal antibodies and inhibiting TRPV1 channels are reasonable strategies to control CHIKV pain.

Original languageEnglish
Article number556
JournalCells
Volume12
Issue number4
DOIs
StatePublished - Feb 2023

Keywords

  • Chikungunya virus
  • E2 envelope protein
  • TRPV1
  • joint pain
  • monoclonal antibody

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