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. 2019 Apr 7;2019:6491738. doi: 10.1155/2019/6491738

Figure 1.

Figure 1

The proposed schematic representation of the immune response to MERS-CoV infection and how the invading virus is processed during an infection. (1) MERS-CoV infects macrophages through DPP4 binding, and then macrophages present MERS-CoV antigens to Th0 cells. This process leads to T cell activation and differentiation, including the production of cytokines associated with the different T cell subsets (i.e., Th1, Th2, and Th17), followed by a massive release of cytokines for immune response amplification. The continued production of these mediators due to viral persistence has a negative effect on Th0, NK, and CD8 T cell activation by inhibiting IL12 and IFN-γ production. However, CD8 T cells produce very effective mediators, such as IFN-γ and granzyme, to clear MERS-CoV. It is still unclear whether long-term or short-term protective antibodies are produced during neutralizing antibody production against MERS-CoV. (2) Attachment of MERS-CoV to DPP4 on the host cell through S protein leads to the appearance of genomic RNA in the cytoplasm. An immune response to dsRNA can be partially generated during MERS-CoV replication. TLR-3 sensitized by dsRNA and cascades of signaling pathways (IRFs and NF-κB activation via TRAF3 and TRAF6, respectively) are activated to produce type I IFNs and proinflammatory cytokines. The production of type I IFNs is important to enhance the release of antiviral proteins for the protection of uninfected cells. Sometimes, accessory proteins of MERS-CoV can interfere with TLR-3 signaling and bind the dsRNA of MERS-CoV during replication to prevent TLR-3 activation and evade the immune response. TLR-4 might recognize S protein and lead to the activation of proinflammatory cytokines through the MyD88-dependent signaling pathway. Virus-cell interactions lead to strong production of immune mediators. The secretion of large quantities of chemokines and cytokines (MCP-1, IL10, and CXCL10) is promoted in infected cells in response to MERS-CoV infection. These chemokines and cytokines in turn recruit lymphocytes and leukocytes to the site of infection. Red arrows refer to inhibitory effects. Black arrows refer to activating effects.