TY - JOUR
T1 - Pathophysiology of chikungunya virus infection associated with fatal outcomes
AU - de Souza, William M.
AU - Fumagalli, Marcilio J.
AU - de Lima, Shirlene T.S.
AU - Parise, Pierina L.
AU - Carvalho, Deyse C.M.
AU - Hernandez, Cristian
AU - de Jesus, Ronaldo
AU - Delafiori, Jeany
AU - Candido, Darlan S.
AU - Carregari, Victor C.
AU - Muraro, Stefanie P.
AU - Souza, Gabriela F.
AU - Simões Mello, Leda M.
AU - Claro, Ingra M.
AU - Díaz, Yamilka
AU - Kato, Rodrigo B.
AU - Trentin, Lucas N.
AU - Costa, Clauber H.S.
AU - Maximo, Ana Carolina B.M.
AU - Cavalcante, Karene F.
AU - Fiuza, Tayna S.
AU - Viana, Vânia A.F.
AU - Melo, Maria Elisabeth L.
AU - Ferraz, Clarissa P.M.
AU - Silva, Débora B.
AU - Duarte, Larissa M.F.
AU - Barbosa, Priscilla P.
AU - Amorim, Mariene R.
AU - Judice, Carla C.
AU - Toledo-Teixeira, Daniel A.
AU - Ramundo, Mariana S.
AU - Aguilar, Patricia V.
AU - Araújo, Emerson L.L.
AU - Costa, Fabio T.M.
AU - Cerqueira-Silva, Thiago
AU - Khouri, Ricardo
AU - Boaventura, Viviane S.
AU - Figueiredo, Luiz Tadeu M.
AU - Fang, Rong
AU - Moreno, Brechla
AU - López-Vergès, Sandra
AU - Mello, Liana Perdigão
AU - Skaf, Munir S.
AU - Catharino, Rodrigo R.
AU - Granja, Fabiana
AU - Martins-de-Souza, Daniel
AU - Plante, Jessica A.
AU - Plante, Kenneth S.
AU - Sabino, Ester C.
AU - Diamond, Michael S.
AU - Eugenin, Eliseo
AU - Proença-Módena, José Luiz
AU - Faria, Nuno R.
AU - Weaver, Scott C.
N1 - Publisher Copyright:
© 2024 The Author(s)
PY - 2024/4/10
Y1 - 2024/4/10
N2 - 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.
AB - 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.
KW - alphavirus
KW - arbovirus
KW - central nervous system infection
KW - chikungunya death
KW - chikungunya virus
KW - hemodynamic disorders
KW - inflammation
KW - mosquito-borne virus
KW - pathophysiology
UR - http://www.scopus.com/inward/record.url?scp=85188991775&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85188991775&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2024.02.011
DO - 10.1016/j.chom.2024.02.011
M3 - Article
C2 - 38479396
AN - SCOPUS:85188991775
SN - 1931-3128
VL - 32
SP - 606-622.e8
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 4
ER -