Artículo
C1q modulation of antibody-dependent enhancement of dengue virus infection in human myeloid cell lines is dependent on cell type and antibody specificity
Byrne, Alana Brooke
; Bonnin, Florencia Agustina; López, Eduardo L.; Polack, Fernando Pedro; Talarico, Laura Beatriz
Fecha de publicación:
06/2024
Editorial:
Elsevier Science
Revista:
Microbes and Infection
ISSN:
1286-4579
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Antibody dependent enhancement (ADE) of dengue virus (DENV) infection is one of the mechanisms contributing to increased severity during heterotypic, secondary infection. The complement protein C1q has been shown to reduce the magnitude of ADE in vitro. Therefore, we investigated the mechanisms of C1q modulation of ADE, focusing on processes of viral entry.Using a model of ADE of DENV-1 infection in human myeloid cell lines in the presence of monoclonal antibodies, 4G2 and 2H2, we found that C1q produced nearly a 40-fold reduction of ADE of DENV-1 in K562 cells, but had no effect in U937 cells. In K562 cells, C1q reduced adsorption of DENV-1/4G2 and exerted a dual inhibitory effect on adsorption and internalization of DENV-1/2H2. Distinct endocytic pathways in the presence of antibody corresponded to conditions where C1q produced a differential action. Also, C1q did not affect the intrinsic cell response mediated by Fc-gammaR in human myeloid cells. The modulation of ADE of DENV-1 by C1q is dependent on the Fc-gammaR expressed on immune cells and the specificity of the antibody comprising the immune complex. Understanding protective and pathogenic mechanisms in the humoral response to DENV infections is crucial for the successful design of antivirals and vaccines.
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Articulos de SEDE CENTRAL
Citación
Byrne, Alana Brooke; Bonnin, Florencia Agustina; López, Eduardo L.; Polack, Fernando Pedro; Talarico, Laura Beatriz; C1q modulation of antibody-dependent enhancement of dengue virus infection in human myeloid cell lines is dependent on cell type and antibody specificity; Elsevier Science; Microbes and Infection; 2024; 6-2024; 1-9
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