Sensing Arboviruses : Dengue and Chikungunya virus

Arboviruses are one of the key health concerns over the past 20 years. There were several outbreaks of arboviruses across the globe which brought attention to some forgotten pathogens. Dengue (DENV) and Chikungunya (CHIKV) viruses are considered re-emerging pathogens as these pathogens expand to new regions and caused large epidemics in South East Asian and Indian Ocean islands. The response of innate immune system towards these viruses are not fully understood especially virus sending by toll-like receptors (TLRs) and the effect of virus infection to innate immune cells such as monocytes. First project has been focused on the DENV interaction with TLRs to induce NF-κB activity. During this research project, we elucidated the mechanism of DENV sensing by TLR2. We demonstrated that DENV can activate NF-κB via TLR2 occurs in a replication independent manner. We also showed that as well TLR2 mediated activation is initiated already at the cell surface. Interestingly, while internalization of the TLR2 and/or the virus increases the level of NF-κB activation, occurs irrespectively of the ability of the virus to fuse from within the endosomal compartment. DENV/TLR2 axis activates NF-κB in a serotype-independent manner, but the ability to activate NF-κB might not be shared between Flaviviruses. Second project has been focused to determine the effect of CHIKV infection on PBMCs and monocyte in context of PBMCs. CHIKV infection increases human peripheral blood mononuclear cells (PBMCs) viability as well as cause the shift of monocyte subsets towards an intermediate phenotype and this effect in not comparable to stimulation with TLR2/4/7 agonists. The effect of CHIKV infection on PBMCs viability and monocyte subset distribution is abolished by pre-treatment of PBMCS with TLR4/7 agonists. However, we were unable to quantify CHIKV infection in PBMCs. In conclusion, we presented a novel role of TLR2 during early host cell interactions with DENV and presented elucidate how CHIKV shapes immune systems response. The obtained knowledge will contribute to the understanding the mechanism of virus induced immunopathology.