Table 3.
Cellular antiviral responses and viral counteractions during Zika infection.
| Cellular Antiviral Responses to Zika Infection | |||
| Cellular Response | Cellular Protein Involved | Molecular Actions and Consequences | References |
| Pro-inflammatory CD8+ T-cell immune response | Cytokines: IL-1β, IL-6, MIP1α; chemokines: IP-10, RANTES | T-cell mediated polyfunctional immune responses with releases of antiviral cytokines and chemokines | [65,103,118,119] |
| CD14+ monocytes and macrophages immune response | CXCL9, CXCL10, CXCL11, CCL5, IL-15 | CD14+ monocytes prime NK cell activities during ZIKV infection | [92] |
| Humoral immune response | IgM, IgG | Production of neutralizing and protective antibodies to ZIKV | [120,121,122] |
| Cellular innate immune response: TLR3-mediated response | TLR3, IRF3, TBK1, type I IFNs, and IFNβ | An early response that triggers IRF3 and recognizes ZIKV dsRNA in cytoplasm leading to activation of type I IFNs and IFNβ production | [57,64,65] |
| Cellular innate immune response: RIG-1/MDA5-mediated response | RIG-1, MDA5, IRF-3, NFkB, type I IFNs, and IFNβ | Late responses that recognize ZIKV dsRNA and contribute to activation of type I IFNs and IFNβ production | [64,65] |
| Type I and type III interferon activation | OAS2, ISG15, MX1 | Production of IFNβ as part of the cellular antiviral responses | [64] |
| Viral Counteraction | |||
| Viral response | Viral protein involved | Molecular actions and consequences | References |
| Counteraction to activation of type 1 IFNs and IFNβ production | NS1, NS2A, NS2B, NS4A, NS4B and NS5 | Targeting RIG-1 pathway | [123,124,125] |
| Inhibition of IFNβ production | NS1, NS4A, NS4B, NS5 | NS4A and NS5 inhibit IRF3 and NFkB; NS1 inhibits IRF3 IFNβ production through binding to TBK1 | [49] |
| Inhibition of the JAK/STAT pathway | NS5, PR | NS5 binds to STAT2 for its proteasomal degradation; PR inhibits JAK1 kinase | [115,126,127] |
| Selective activation of type II IFN signaling | NS5 | NS5 promotes the formation of STAT1/STAT1 homodimers and activates type II IFN for viral replication | [123] |
| Induction of cellular autophagy | prM, M, NS1, NS2A, NS4A | In a yeast study, these ZIKV proteins induced cellular autophagy as indicated by formation of cytoplasmic puncta | [9] |
| Induction of cellular autophagy | NS4A, NS4B | Inhibit Akt-mediated mTOR pathway through Tor1/TSC1 and Tip41 | [9,111] |