Introduction to Interferons
- Interferons are low molecular weight protein, produced by virus infected cells.
- These, itself induces the formation of a second protein inhibiting the transcription of viral mRNA.
- These are produced by the host cell in response to the virus particle, viral nucleic acid and non-viral agents.
- Non-viral agents include synthetic polynucleotides such as polyinosinic acid and polycytidylic acid (poly I:C).
- These are a family of natural glycoproteins which inhibits viral replication.
- Isaacs and Lindermann discovered interferon in 1957.
Image source: mdpi
A) Types of interferons
- There are three antigenically and chemically distinct types of interferon. They are:
i) Type I interferons
- These are acid-stable and produced by monocytes and B lymphocytes.
- These comprise two major classes, leukocyte interferon (Le-IFN, IFN-alpha) released by stimulated leucocytes, and fibroblast interferon (F-IFN, IFN-beta) released by stimulated fibroblasts.
- These have maximal antiviral activity.
- These induce viral resistant state in human cells.
ii) Type II interferons
- These are acid-labile and are also known as ‘immune’ (IFN-gamma) interferons because they are produced by T lymphocytes in the cellular immune system in response to specific antigen.
- These are more active in inhibiting growth of tumour cells.
- These have intermediate antiviral activity.
- These are more active as a lymphokine than as an antiviral agent.
Image source: biorender
B) Chemical nature and formation
- They are glycoprotein in nature with molecular weight 20,000 to 40,000.
- They do not contain any nucleic acid and are nontoxic and non-antigenic.
- They can withstand heating at 370C for 30 to 60 minutes.
- These are inactivated by proteolytic enzymes.
- Interferon α and interferon β share many properties, including structural homology and mechanism of action.
- Interferon α is produced by B lymphocytes, monocytes and macrophages.
- Interferon β is produced by fibroblasts and other cells in response to viral infections and other stimuli.
- Interferon γ is produced by activated T lymphocytes and NK cells in the later part of infection. It is also called macrophage activation factor.
Image source: frontiers
YOU MAY ALSO WANT TO READ ABOUT: Protein types and it’s function
- Interferons have antiviral properties in adjacent, non-infected cells (as opposed to in infected cells).
i) Species specific
- Interferon produced by one species can protect only cells of the same or related animal species against viral infection.
- Thus, interferon produced by mouse cell in tissue culture is active only on other mouse cells but without any effect in chicken cells.
- Interferon activity is not virus specific.
- Interferon induced by non-virus (non-viral inducers) render cell resistant to infection by the same or unrelated broad spectrum of viruses.
iii) Virus susceptibility
- Though all viruses are inhibited by interferon, but RNA viruses are more susceptible to interferon.
iv) Relation to recovery
- During the acute phase of disease, interferon α and β combat viral multiplication and is probably responsible for recovery.
D) Mechanism of action
- Synthesis of IFN- α and IFN- β begin with an hour of infection and attains maximum level in 6-12 hours.
- Once synthesized, the interferons bind to specific receptors on uninfected neighbouring cells in which they inhibit viral replication.
- Inhibition of replication of virions by interferon is mediated by cellular enzymes expression of which is regulated by interferons.
- These antiviral proteins are not, however, activated until they bind to double stranded RNA.
I) Type I interferons
- They inhibit viral protein synthesis, but cellular protein synthesis is not affected.
- They inhibit viral protein synthesis by activating the under mentioned enzyme.
- Two oligo-A adenylate synthetases which, in the presence of ds-RNA, synthesize an adenine nucleotide 2’- 5’ phosphordiester linkages.
- The linkage product digests viral mRNA.
- A 68kd protein kinase in presence of ds-RNA inactivates elongation factor-2 (EF-2) and blocks protein synthesis.
- Type I interferons may block viral replication in some other stages, including budding.
II) Type II interferons
- IFN- γ also possesses antiviral activity.
- Induction of nitric oxide synthetase causes increase in intracellular nitric oxide concentration leading to inhibition of viral replication.
Upregulation of MHC-I and MHC-II expression
- IFN- γ enhances the activation and effector function of cytotoxic T cells capable of destroying virus infected cells.
Activation and cytotoxicity
- IFN- γ also enhances the activation of the monocytes, macrophages and NK cells which are capable of killing virus-infected cells by non-immune mechanisms.
Interferons: types, chemical nature, properties and mechanism of action