Here is a complete 5-marker answer on the Mode of Action of Viral Interferons:
Viral Interferon - Mode of Action
(Medical Microbiology 9e; Sherris & Ryan's Medical Microbiology, 8e)
The 5-Step Mechanism (Exam Answer)
Step 1 - Induction & Release
A virus-infected cell (or plasmacytoid dendritic cell) detects double-stranded RNA (dsRNA) produced during viral replication. This is the major trigger for synthesis and release of IFN-α and IFN-β (Type I interferons) within hours of infection. A single dsRNA molecule per cell is sufficient to trigger this response.
Step 2 - Binding to Neighbouring Cells
Released interferon does not protect the already-infected cell. Instead, it binds to specific cell-surface receptors (IFNAR) on uninfected neighbouring cells via JAK/STAT signalling. This is the "early warning system" for surrounding cells.
Step 3 - Establishment of the "Antiviral State"
Via JAK-STAT signalling, interferon upregulates the synthesis of three key antiviral proteins inside the neighbouring cell:
- Protein Kinase R (PKR)
- 2',5'-Oligoadenylate Synthetase (OAS)
- Mx protein (especially important for influenza)
These proteins are produced but remain inactive until dsRNA is detected inside that cell (i.e., until that cell itself becomes infected).
Step 4 - Activation by Viral dsRNA & Enzymatic Cascades
When that cell is subsequently infected, viral dsRNA activates the antiviral enzymes through two parallel pathways:
| Pathway | Enzyme | Mechanism |
|---|
| Pathway 1 | PKR | Phosphorylates eIF-2α (elongation initiation factor) → blocks ribosome assembly → inhibits protein synthesis |
| Pathway 2 | OAS → RNase L | 2',5'-OAS synthesizes 2',5'-oligoadenylate → activates RNase L → degrades viral mRNA |
| Pathway 3 | Mx protein | Blocks influenza by inhibiting viral transcription directly |
Step 5 - Immune Activation & Systemic Effects
Interferons also amplify immune defenses:
- Activate NK cells for early killing of infected cells
- Upregulate MHC class I on cell surfaces → better antigen presentation → enhanced killing by cytotoxic T lymphocytes (CTLs)
- Trigger systemic flu-like symptoms (fever, myalgia, malaise) via hypothalamic effects
Diagrams
Fig 1 - Induction of antiviral state (Medical Microbiology 9e):
Fig 2 - Dual pathway cascade (Sherris & Ryan's Medical Microbiology 8e):
Key Points for 5 Markers
- Interferon does NOT directly block virus - it induces a protective state in uninfected cells
- dsRNA is the key trigger for both interferon production AND activation of antiviral enzymes
- Two main enzymatic pathways: PKR (protein synthesis inhibition) + OAS/RNase L (mRNA degradation)
- Mx protein is specifically relevant to influenza
- The antiviral enzymes remain latent in uninfected cells - dsRNA from active infection is required to switch them on (prevents damage to healthy uninfected cells)
Sources: Medical Microbiology 9e (Sherris & Ryan), Ch. 10; Sherris & Ryan's Medical Microbiology 8e, Ch. 7