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Activation of TLR2 and TLR6 by Dengue NS1 Protein and Its Implications in the Immunopathogenesis of Dengue Virus Infection


Despite the prevalence of dengue virus infection and the heavy economic burden it puts on the endemic countries, the immunopathogenesis of dengue virus infection remains unclear. Plasma leakage in dengue hemorrhagic fever (DHF) develops not when the viremia is at its peak in infected patients but when viremia has been significantly reduced or cleared. This suggests that host immune response is responsible for the development DHF. The interactions of the viral factors with host factors which trigger the host immune responses are likely to play a significant role in the development of dengue diseases, thus are of great interests. In this study, we found that dengue NS1 protein activates TLR2 and TLR6, leading to increase proinflammatory cytokine production. In addition, the interaction of viral factor with TLR6 was found to play an important role in the manifestation of dengue virus infection. Our study provides new insights into the involvement of TLR6 in dengue virus infection and the potential of using TLR6 anatagonist in therapeutic treatment for DV infection.


Vyšlo v časopise: Activation of TLR2 and TLR6 by Dengue NS1 Protein and Its Implications in the Immunopathogenesis of Dengue Virus Infection. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1005053
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005053

Souhrn

Despite the prevalence of dengue virus infection and the heavy economic burden it puts on the endemic countries, the immunopathogenesis of dengue virus infection remains unclear. Plasma leakage in dengue hemorrhagic fever (DHF) develops not when the viremia is at its peak in infected patients but when viremia has been significantly reduced or cleared. This suggests that host immune response is responsible for the development DHF. The interactions of the viral factors with host factors which trigger the host immune responses are likely to play a significant role in the development of dengue diseases, thus are of great interests. In this study, we found that dengue NS1 protein activates TLR2 and TLR6, leading to increase proinflammatory cytokine production. In addition, the interaction of viral factor with TLR6 was found to play an important role in the manifestation of dengue virus infection. Our study provides new insights into the involvement of TLR6 in dengue virus infection and the potential of using TLR6 anatagonist in therapeutic treatment for DV infection.


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