What is Anti-Viral Response?

[biologist]

Is it intracellular mechanism? And what cell types are involved?

[admin]

Immune system is a collection of mechanisms within the organism that allow protection against foreign particles such as pathogens, bacterial infections, and viruses. Human immune system is usually divided into two functional categories: innate immune response and adaptive immune response. Innate immune system response is immediate, but non-specific – it usually involves the following features:

1. Induction of inflammation
2. Activation of complement system
3. Intracellular induction of TNF-alpha, Interferon and Interleukin/Cytokines genes
4. Recruiting phagocytes (macrophages, neutrophils, and dendritic cells), mast cells, eosinophils, basophils, and natural killer (NK) cells to identify and eliminate pathogens, either by attacking larger pathogens through contact or by engulfing and then killing microorganisms.

On the other hand, adaptive immune system response is activated by the innate response and immune system adapts its response during an infection to improve its recognition of the pathogen or infection. This improved response of the adaptive immune system is then retained after the infection has been eliminated, in the form of an immunological memory (memory T-cells).

Intracellular antiviral response

The innate immunity includes intracellular virus recognition and induction of initial anti-viral responses. For example, many RNA viruses are recognized by retinoic acid-inducible gene I (RIG-I)-like helicases (RLHs) and Toll-like receptors (TLRs). Such molecular identification leads to induction of anti-viral response signaling pathway. Intracellular antiviral response involves different set of genes and signaling pathways depending on the mechanism that virus use to infect the cell, as well as what cell type is being infected (for example, the Hepatitis virus mainly effects liver cells, while Epstein-Barr virus infects lymphocytes). However, intracellular mechanism of antiviral response for the majority of known viral infections includes induction of type I interferon (Interferon-alpha and Interferon-beta synthesis) and pro-inflammatory cytokines, as well as activating set of genes from the “anti-viral response signaling pathway”

[ATGC2001]

Great review article by S.Goodbourn et al "Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures " http://vir.sgmjournals.org/cgi/content/full/81/10/2341

[admin]

Induction of type I interferon (IFN) expression is major phenotype of the innate immune response against viral infection. Upon molecular recognition of specific components of the virus - host cell activates various signaling cascades that induce an innate antiviral response. This result in the disruption of viral replication and increased activity of the adaptive arm of the immune system. So, again - major event in antiviral response is the production of type I interferons (IFNs) - a family of immunoregulatory proteins.

[transfection]

JAK/STAT Pathway is important mechanism in anti-viral response. JAKs possess two nearly identical phosphate-transferring domains, an active kinase domain (JH1) and a catalytically inactive pseudokinase domain (JH2).

JH1: catalytic tyrosine kinase; tyrosine residues in the activation loop region, GXGXXG motif in the nucleotide-binding loop: conserved aspartic acid residue involved in the phosphotransfer reaction in the catalytic loop.

JH2: lacks characteristic residues of active tyrosine kinases, making it catalytically inactive

Activation loop region: JAKs require phosphorylation of residues in their activation loop for full activity. Contaln an YY motif in their activation loop.
Cross-phosphorylated by JAK upon dimerization/oligomerization of their associated receptor

Catalytic Loop: Phosphorylates the cytokine receptor and STATs.