Interferons: types, chemical nature, properties and mechanism of action

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.

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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.


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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.

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C) Properties

  • 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.

ii) Non-specificity

  • 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