Background: There is a lack of specific antiviral therapy against dengue virus (DENV) in current use. Therefore, a great proportion of dengue cases progress to severe clinical forms due to a complex interplay between virus and host immune response. It has been hypothesized that heterotypic non-neutralizing antibodies enhance DENV infection in phagocytic cells, and this induces an inflammatory response that is involved in the pathogenesis of severe dengue. Purpose: To identify the antiviral and immunomodulatory effects of polyphenols on dengue virus infection. Methods: Human U937-DC-SIGN macrophages were infected with DENV serotypes 2 or 3 in the presence or not of enhancing antibody 4G2. Viral titers and the secretion of tumor necrosis factor-alpha, IL-6, IL-10 and interferon-alpha were analyzed timely. Results: DENV infection alone induced high production of IL-6 and TNF-α, but in the presence of 4G2 antibody, viral titers and TNF-α secretion were potentiated. Based on antiinflammatory antecedents, the polyphenols curcumin, fisetin, resveratrol, apigenin, quercetin and rutin were tested for antiviral and immunomodulatory properties. Only quercetin and fisetin inhibited DENV-2 and DENV-3 infection in the absence or presence of enhancing antibody (>90%, p<0.001); they also inhibited TNF-α and IL-6 secretion (p<0.001). Conclusion: Quercetin and fisetin down-regulate the production of proinflammatory cytokines induced by DENV infection enhanced by antibodies a mechanism involved in severe dengue.
Bibliographical noteFunding Information:
This work was supported by Mexican Institute of Social Security “IMSS” (grants FIS/IMSS/PROT/G17-2/1732 and CTFIS/10RD/12/2011) and by Secretary of Public Education – Redes temáticas (BUAP-CA-147). Carolina Jasso-Miranda had scholarships from National Council of Science and Technology CONACYT (No. 374373) and IMSS (98224279). Julio Reyes-Leyva has a research fellowship from Fundación IMSS A.C. None of these institutions participate, determine or interfere in any form with the design and development of the study, decision to publish or preparation of the manuscript.
© 2019 Jasso-Miranda et al.
- Enhancing antibody
- Proinflammatory cytokines