The eIF-2a protein kinase system

Intracellular replication of viral particles entirely depends upon successful intracellular transcription of viral genes with subsequent translation of the viral mRNA. Translation of viral or cellular mRNA is dependent upon ribosome formation. Normally several constituent molecules interact with each other on the mRNA transcript, forming the smaller ribosomal subunit. Subsequent formation/attachment of the larger subunit facilitates protein synthesis. 

Induction of eIF-2a protein kinase is dependent upon both IFN type and cell type. IFN-a, -jS and -y are all known to induce the enzyme in various animal cells. However, in human epithelial cells the kinase is induced only by type I IFNs, while none of the IFNs seems capable of inducing synthesis of the enzyme in human fibroblasts. The purified kinase is highly selective for initiation factor eIF-2, which it phosplorylates at a specific serine residue. 

Interferon, in particular type I IFN, is well adapted to its anti-viral function. Upon entry into the body, viral particles are likely to quickly encounter IFN-a/jS-producing cells, including macrophages and monocytes. This prompts IFN synthesis and release. These cells act like sentries, warning other cells of the viral attack. Most body cells express the type I IFN receptor, thus the released IFN-a or will induce an anti-viral state in such cells. 

The ability of IFNs (especially type I IFNs) to induce an anti-viral state is unlikely to be solely dependent upon the enzymatic mechanisms discussed above. Furthermore, the 2 -5 A synthetase and eIF-2a kinase systems may play important roles in mediating additional IFN actions. The ability of such systems to stall protein synthesis in cells may play a role in IFN-induced alterations of cellular differentiation or cell cycle progression. They may also be involved in mediating IFN-induced anti-proliferative effects on various transformed cells. 

Major histocompatibility complex (MHC) antigens and )S2-macroglobulin are amongst the best known proteins whose synthesis is also induced in a variety of cell types in response to various interferons. 

Induction of eIF-2a protein kinase is dependent upon both interferon type and cell type. 

IFN binds its receptor, inducing synthesis of elF-2 protein kinase 

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Figure 8.6 Outline of how the eIF-2a protein kinase system promotes an antiviral effect...

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