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Pathophysiology of chikungunya virus infection associated with fatal outcomes

2024; Cell Press; Volume: 32; Issue: 4 Linguagem: Inglês

10.1016/j.chom.2024.02.011

1934-6069

William Marciel de Souza, Marcílio Jorge Fumagalli, Shirlene Telmos Silva de Lima, Pierina Lorencini Parise, Deyse Cristina Madruga Carvalho, Cristián E. Hernández, Ronaldo de Jesus, Jeany Delafiori, Darlan S. Candido, Victor Corasolla Carregari, Stéfanie Primon Muraro, Gabriela Fabiano de Souza, Leda Maria Simões Mello, Ingra Morales Claro, Yamilka Díaz, Rodrigo Bentes Kato, Lucas N Trentin, Clauber Henrique Souza da Costa, Ana Carolina Barjud Marques Máximo, Karene Ferreira Cavalcante, Tayná da Silva Fiúza, Vânia A.F. Viana, Maria Elisabeth L Melo, Clarissa Perdigão Mello Ferraz, D. B. da Silva, Larissa M F Duarte, Priscilla P. Barbosa, Mariene R. Amorim, Carla C. Judice, Daniel A. Toledo-Teixeira, Mariana Severo Ramundo, Patricia V. Aguilar, Emerson Araújo, Fábio Trindade Maranhão Costa, Thiago Cerqueira‐Silva, Ricardo Khouri, Viviane Boaventura, Luíz Tadeu Moraes Figueiredo, Rong Fang, Brechla Moreno, Sandra López‐Vergès, Liana Perdigão Mello, Munir S. Skaf, Rodrigo Ramos Catharino, Fabiana Granja, Daniel Martins‐de‐Souza, Jessica A. Plante, Kenneth S. Plante, Éster Cerdeira Sabino, Michael Diamond, Eliseo Eugenin, José Luiz Proença‐Módena, Nuno R. Faria, Scott C. Weaver,

Viral Infections and Vectors

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.