3.3 Cytosolic receptors for viral infection

After a virus has escaped from the endosome of an infected cell, virus components are located in the cytoplasm. Receptors are also present in the cytoplasm, that recognise and limit viral replication and spread. They belong to a family of receptors called the ‘Retinoic acid-inducible gene I (RIG1)-like helicases’ which are understandably abbreviated to RLHs. Two receptors are particularly important in this context:

• RIG-1 itself which recognises short dsRNA
• MDA5 which recognises long dsRNA

After binding to dsRNA these receptors localise to mitochondria via an adapter protein IPS-1. They then activate transcription factors NFκB and IRF3 (Interferon regulatory protein-3) which translocate to the nucleus of the cell and activate transcription of a number of genes including the genes for type-1 interferon, as shown in Figure 11. You can also see that RIG-1 and MDA5 are cytoplasmic receptors for dsRNA. They lead to activation of transcription factors IRF3 and NFκB, which promote transcription of genes for type 1 interferons, and other cytokines

Figure 11 Recognition of viral dsRNA.

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The diagram shows the intracellular pathways by which virus is recognised and interferon synthesis initiated. Viral dsRNA is recognised by cytosolic receptors RIG-1 and MDA5, which interact with mitochondrion-associated IPS-1 causing activation of transcription factors IRF3 and NFκB, which translocate to the nucleus to initiate transcription of genes encoding type-1 interferons.

Figure 11 Recognition of viral dsRNA.