(ns, non-significant; * 0

(ns, non-significant; * 0.05; ** 0.01; *** 0.001). Raw cells were inoculated with CHIKV in the presence of SB, SP, or solvent control DMSO as described above. corresponding mock cells. Further, it was demonstrated that CHIKV mediated TNF production in the macrophages is dependent on p38 and JNK MAPK pathways linking p-c-jun transcription factor. Interestingly, it was found that CHIKV nsP2 interacts with both p-p38 and p-JNK MAPKs Protirelin in the macrophages. This observation was supported by the protein-protein docking analysis which illustrates the specific amino acids responsible for the nsP2-MAPKs interactions. A strong polar interaction was predicted between Thr-180 (within the phosphorylation lip) of p38 and Gln-273 of nsP2, whereas, no such polar interaction was Protirelin predicted for the phosphorylation lip of JNK which indicates the differential roles of p-p38 and p-JNK during CHIKV infection in the host macrophages. In summary, for the first time it has been shown that CHIKV triggers robust TNF production in the host macrophages via both p-p38 and p-JNK/p-c-jun pathways and the interaction of viral protein, nsP2 with these MAPKs during infection. Hence, this information might shed light in rationale-based drug designing strategies toward a possible control measure of CHIKV infection in future. or mosquito. CHIKV mediated disease is one of the global challenges due to its endemics in different parts of the world (103 countries), such as Tanzania (1C3), Reunion island (4C7), India (8C12), Italy (13, 14), and Thailand (15C18). Among Alphaviruses, CHIKV is considered as one of the most successfully evolved virus. The Arboviruses including CHIKV have been evolving and re-emerging from centuries and their emergence and dispersion are more rapid and geographically extensive. This might be due to increase in global communication, mass immigration, vector adaptation to urbanization and land perturbation (19). Even though mortality due to CHIKV is very rare and restricted to children’s (below 1 year), old age (above 65 years) or immune compromised patients, Rabbit Polyclonal to OR2Z1 the pathogenesis (mainly inflammatory responses) may persist for very long periods of time both in humans and macaque model (20, 21). Currently, arboviruses raise a serious threat to the global public health, due to unavailability of effective drugs or vaccines (22, 23). Recent studies on CHIKV induced immune responses suggest that the host immune system is found to be both beneficiary in one hand by controlling viral infection, whereas deleterious on the other hand by promoting severe inflammatory responses (24C28). Studies have shown that CHIKV induces different inflammatory cytokines/chemokines (TNF, IL-1, IL-6, IFN-, IL-8, and MCP-1) (24, 29C37), which might be associated with arthritis like pathogenesis during CHIKV infection. In different systems (both mouse and non-human primates), predominant cellular infiltration of macrophages, monocytes, Protirelin NK cells and T cells to the site of inoculation and other tissues have been observed (38, 39). Moreover, immunohistochemistry and flow cytometry based analysis of muscles and synovial biopsies revealed that macrophages are major infiltrating cells among MPS (mononuclear phagocytic system) (25, 40). Blood monocytes and tissue macrophages are the major immune cells infected by CHIKV (21, 31, 41). In macaque, synovial macrophages have been identified as the major host cell for long-term viral persistence (21). This productive infection of CHIKV in the host macrophages might be associated with arthritis like pathogenesis despite robust immune activation (41, 42). T cell immune responses specific to CHIKV is not clearly understood yet. Teo TH et al. have suggested that CD4+ T cells (but not CD8+ T cells) are essential for the development of CHIKV induced pathogenesis without affecting virus infection and dissemination in mice and this is independent of IFN- (43). Flow cytometry based analysis of circulating lymphocytes Protirelin in CHIKV patients confirms that there are both CD4+ and CD8+ T cell responses during early and late phases of infection, respectively. Moreover, CD95 mediated apoptosis was also detected in CD4+ T cells after 2 days of symptom appearance (44), which might be one of the strategies to evade host immunity. Purified T cells (both CD4+ and CD8+) from the.