Potential of Interleukin (IL)-12 Group as Antivirals: Severe Viral Disease Prevention and Management

Figure 1. Activation of CD4+ T cells and IFN-γ pathway via IL-12 signalling. (a) Upon binding to cell receptors, IL-12 initiates the proliferation of CD4+ T cells into Th-1 cells that subsequently activates immune effectors to further enhance host defence against virus infections. Eventually, clearance of virus particles and infected cells can be carried out by the host immune system. Secondly, the activated Th-1 cells also synthesize IFN-γ via Jak/STAT signalling. The release of IFN-γ into the surroundings encourages the proliferation and activation of macrophages and NK T cells. (b) NK T cells are important cellular effectors in eliminating infected cells. (c) Once armed, macrophages actively engulf virus particles to prevent virus spread. The dashed-line arrows represent the antiviral activities.

Figure 2. IL-23 activity in NK cells. IL-23 (p40/p19) binds to its receptor on the surface of NK cells. The binding leads to the production of effector IFN-γ. IFN-γ is responsible for promoting CD8+ T-cell responses such as eliminating infected cells in a perforin-dependent manner. The targeted cell undergoes programmed cell death, preventing spread of the virus.

Figure 3. Pro-inflammatory reactions by IL-23. (a) IL-23 induces the expression of immune effectors. Upon their expressions, those effectors enhance the host immune response, which subsequently elevates virus clearance. (b) IL-23 limits anti-inflammatory activities (dashed-line arrows) via the downregulation of Treg. It later increases the pro-inflammatory response that aids in the removal of virus particles.

Figure 4. Anti-inflammatory and antiviral actions of IL-35. (a) IL-35 induces the proliferation of Treg in order to suppress the synthesis of pro-inflammatory cytokines. The inhibition subsequently improves inflammation and tissue damage that are usually manifested as the severity of virus infections. (b) IL-35 controls the maturation of naïve CD8+ T cells into cytotoxic T cells. The limiting number of mature cytotoxic T cells prevents the occurrence of cellular damage. (c) IL-35 induces antiviral effects via interferon production. Interferons are known to inhibit viral protein synthesis, genome replication and assembly. The inhibitory activities prevent virus replication and limit virus spreading. The dashed-line arrows represent inhibitory effects.

Figure 5. IL-27-mediated antiviral response in infected cells. (a) IL-27 triggers the production of effector mediators and chemokines to promote inflammation. These mediators enhance the host immune response in its targeting of virus infections, for example antigen presentation, cell apoptosis, synthesis of pro-inflammatory cytokines and infiltration of immune cells. Those pro-inflammatory reactions are responsible for virus clearance. (b) In order to control the occurrence of pro-inflammations in infected cells, IL-27 promotes the formation of Treg cells that execute anti-inflammatory responses in the host. Treg controls T-cell-mediated inflammation in order to prevent undesired immune-mediated complications. (c) Upon binding to receptors, IL-27 activates STAT signalling pathways. The activation of STAT signalling results in the transcription and translation of antiviral products that help target virus replication. The dashed-line arrows indicate inhibitory actions on cellular inflammation and the synthesis of new virus progeny.