Pathophysiology of chikungunya virus infection associated with fatal outcomes

William M. de Souza, Marcilio J. Fumagalli, Shirlene T.S. de Lima, Pierina L. Parise, Deyse C.M. Carvalho, Cristian Hernandez, Ronaldo de Jesus, Jeany Delafiori, Darlan S. Candido, Victor C. Carregari, Stefanie P. Muraro, Gabriela F. Souza, Leda M. Simões Mello, Ingra M. Claro, Yamilka Díaz, Rodrigo B. Kato, Lucas N. Trentin, Clauber H.S. Costa, Ana Carolina B.M. Maximo, Karene F. CavalcanteTayna S. Fiuza, Vânia A.F. Viana, Maria Elisabeth L. Melo, Clarissa P.M. Ferraz, Débora B. Silva, Larissa M.F. Duarte, Priscilla P. Barbosa, Mariene R. Amorim, Carla C. Judice, Daniel A. Toledo-Teixeira, Mariana S. Ramundo, Patricia V. Aguilar, Emerson L.L. Araújo, Fabio T.M. Costa, Thiago Cerqueira-Silva, Ricardo Khouri, Viviane S. Boaventura, Luiz Tadeu M. Figueiredo, Rong Fang, Brechla Moreno, Sandra López-Vergès, Liana Perdigão Mello, Munir S. Skaf, Rodrigo R. Catharino, Fabiana Granja, Daniel Martins-de-Souza, Jessica A. Plante, Kenneth S. Plante, Ester C. Sabino, Michael S. Diamond, Eliseo Eugenin, José Luiz Proença-Módena, Nuno R. Faria, Scott C. Weaver

Research output: Contribution to journalArticlepeer-review


Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that causes acute, subacute, and chronic human arthritogenic diseases and, in rare instances, can lead to neurological complications and death. Here, we combined epidemiological, virological, histopathological, cytokine, molecular dynamics, metabolomic, proteomic, and genomic analyses to investigate viral and host factors that contribute to chikungunya-associated (CHIK) death. Our results indicate that CHIK deaths are associated with multi-organ infection, central nervous system damage, and elevated serum levels of pro-inflammatory cytokines and chemokines compared with survivors. The histopathologic, metabolite, and proteomic signatures of CHIK deaths reveal hemodynamic disorders and dysregulated immune responses. The CHIKV East-Central-South-African lineage infecting our study population causes both fatal and survival cases. Additionally, CHIKV infection impairs the integrity of the blood-brain barrier, as evidenced by an increase in permeability and altered tight junction protein expression. Overall, our findings improve the understanding of CHIK pathophysiology and the causes of fatal infections.

Original languageEnglish
Pages (from-to)606-622.e8
JournalCell Host and Microbe
Issue number4
StatePublished - Apr 10 2024

Bibliographical note

Publisher Copyright:
© 2024 The Author(s)


  • alphavirus
  • arbovirus
  • central nervous system infection
  • chikungunya death
  • chikungunya virus
  • hemodynamic disorders
  • inflammation
  • mosquito-borne virus
  • pathophysiology

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Virology


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