NATURAL CYTOSTASIS

Interferons


Interferons (IFNs) are cytokines, which are secreted by a variety of cell types under the influence of some inducers such as viral envelope glycoproteins, CpG DNA, dsRNA and other Pathogen-Associated Molecules Patterns (PAMPs) as well as Tumor-Associated Molecular Patterns (TAMPs).

Type I interferons, IFN-α and IFN-β, are produced by many cell types including lymphocytes (NK cells, B cells, and T cells), macrophages, dendritic cells, fibroblasts, endothelial cells, osteoblasts and others, and exhibit powerful antiviral and antitumor effects. They also stimulate NK cells to elicit an antiviral and antitumor response. Besides, IFN-α acts as a pyrogenic and painful factor by affecting thermosensitive neurons in the hypothalamus that causes fever and pain. On the other hand, IFN-α interacts with the μ-opioid receptor to act as an analgesic. To affect a target cell, IFN-α and IFN-β use the CD118 molecule as the receptor.
Type II IFN-γ is produced by activated T cells, B cells, and NK cells, and also exerts some antiviral and antitumor effects but these effects are generally weaker than those of IFN-α and IFN-β exhibit. However, IFN-γ is a potent immunoregulatory cytokine, which functions in a synergic manner with TNF-α, TNF-β, IL-1β, IL-6, and other cytokines and chemokines, and is extremely important for almost all immune processes. The CD119 molecule is the receptor for IFN-γ.

To date, several effector pathways of the IFN-mediated antiviral response have been described. IFN-inducible enzymes inside a cell infected by a virus individually block viral transcription, degrade viral RNA, inhibit translation, and control all steps of viral replication. As a result, natural cytostasis takes place.
The main effector pathways of the IFN-mediated antiviral response are as follows:

Protein Kinase R (PKR);
2',5'-oligoadenylate-synthetase (OAS) with the participation of ribonuclease L (RNase L), and
Mx protein GTPases.

Protein Kinase R (PKR), an RNA dependent protein kinase, inhibits the translation of viral proteins through phosphorylation of protein synthesis initiation factor eIF-2α. 2',5'-oligoadenylate-synthetase (OAS) mediates RNA degradation. For this process, the 2nd enzyme, ribonuclease L (RNase L), is required, which becomes activated by binding 25A oligonucleotides. In addition, Mx-protein-GTPases appear to target viral nucleocapsids and inhibit RNA synthesis. The Mx protein alone is sufficient to block the replication of the virus in the absence of any other IFN-α/IFN-β-inducible enzymes, but the Mx protein is not induced by IFN-α.

Among such cytokines as IL-2, IL-12, IL-15, IL-18, and CCL5 (RANTES), IFNs are also powerful activators of NK cells.

©V.V.Klimov