PMC:7647877 / 7001-9871 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/7647877","sourcedb":"PMC","sourceid":"7647877","source_url":"https://www.ncbi.nlm.nih.gov/pmc/7647877","text":"The binding of the cytokine to its transmembrane cell surface receptor activates an intracellular signal transduction pathway, generally a Janus kinase (Jak), which, via a kinase cascade, phosphorylates its transcription protein (STAT). Phosphorylated STAT dimers and moves to the nucleus, initiating a new gene transcription. Mutation of STAT1 increases susceptibility to virus infections because it is involved in various signalling pathways, including IFN-α/β, IFN- γ, IFN-l, IL-2, IL-3, IL-6, IL-9, IL-10, IL-11, IL-12, IL-15, IL-21, IL-22, IL-26 and IL-27 [10], and chemokines of several types such as C-X-C motif chemokine ligand 10 (CXCL-10), Regulated upon Activation, Normal T Cell Expressed and Presumably Secreted (RANTES)/Chemokine (C–C motif) ligand 5 (CCL-5), Monocyte Chemoattractant Protein-1 (MCP-1) [11]. IFN-γ promotes antigen-specific antibody production, increasing the activity of phagocytosis. In the meantime, PRRs trigger inflammatory signalling, with activation of transcription factors like nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB). NFκB is the key transcriptional regulator of many pro-inflammatory cytokines, adhesion molecules, chemokines, growth factors and other mediators of inflammation, as tumour necrosis factor (TNF), interleukins 1 (IL-1β), 6 (IL-6), and 12 (IL-12), promotes cellular proliferation and protects against apoptosis providing a mechanism that determines chronic inflammation. The recognition of pathogens is achieved through the presence of pattern recognition receptors (PRRs) [12]. PRRs identify the microbe-associated molecular patterns (MAMPs), and defensive responses is activated. PRRs include Toll-like receptors (TLRs), that are able to recognize viral DNA, viral double-stranded RNA and viral single-stranded RNA. TLRs are expressed on macrophages, dendritic cells, neutrophils, eosinophils, epithelial cells and keratinocytes. In particular, intracellular TLR-7 and TLR-8 allow the innate recognition of the single-stranded RNA of coronaviruses [13]. Intracellular and extracellular PRRs recognized spike glycoprotein, of the coronavirus coat, starting the inflammatory process, through the NFκB pathway [14]. Moreover, Nucleotide-Binding Domain, Leucine-Rich Repeat (NLR) proteins have also been identified, and NALP3 (NACHT, LRR and PYD domains-containing protein 3) has a special function in the innate immune response [15]. The processes involved in antiviral immunity is shown in Fig. 1.\nFig. 1 Graphical representation of antiviral SARS-Coronavirus 2 immunity. B: B lymphocyte; CTL: cytotoxic; T lymphocyte; IFN: interferon; Ig: immunoglobulin; IL: interleukin; MHC: major histocompatibility class; NFκB: nuclear factor kappa-light- chain- enhancer of activated B cells; NK: natural killer cell; Th: helper T lymphocyte; TLR: Toll-like receptor; TNF: tumour necrosis 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