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INTERFERON
The name "interferon" was given by Issacs and Lindenmann
after they were recognized by their ability to interfere with viral
replication.
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Interferons are natural cellular products released
from infected host cells in response to viral or other foreign
nucleic acids. They are detectable as early as 2 h after
infection.
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Interferons can be produced by all vertebrate
species.
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They are host specific but not virus
specific.
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Normal cells don't synthesize interferons until
induced to do so.
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RNA viruses are strong inducers than DNA
viruses.
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They are considered to be body's first line of
defense against viral infections.
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Antiviral state induced by interferons last only
for few days.
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Interferons are highly potent, <50 molecules
per cell are sufficient to induce anti-viral state.
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There are three types of interferons, IFN-a, IFN-�
and IFN-gamma. They are all coded by different genes and are not
related antigenically.
Properties of interferons:
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Property
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Alpha
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Beta
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Gamma
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Current nomenclature
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IFN-α
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IFN-β
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IFN-γ
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Former designation
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Leucocyte
interferon (Type I interferon)
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Fibroblast
interferon (Type I interferon)
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Immune
interferon
(Type
II interferon)
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No. of genes coding
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≥15
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1
or few
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1
or few
|
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No. of subtypes
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20
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2
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3
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Principal cell source
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Leucocytes
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Fibroblasts
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Lymphocytes
and NK cells
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Inducing agent
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Viruses,
dsDNA
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Viruses,
dsDNA
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Mitogens
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Size (MW)
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17,000
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17,000
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17,000
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No. of amino acids
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143
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145
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146
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Introns in genes
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No
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No
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Yes,
3
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Chromosomal location
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9
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9
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12
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Stability at pH 2
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Stable
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Stable
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Labile
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Glycosylation
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No
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Yes
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Yes
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Antiviral activity of interferons:
Interferons bind to cell surface receptors. IFN-a and IFN-�
share a common receptor while IFN-gamma has a distinct receptor. This
binding triggers tyrosine phosphorylation and finally transcription of
at least two enzymes that block viral reproduction by inhibiting the
translation of viral mRNA.
Other possible mechanisms are:
- Inhibits penetration and uncoating of SV40 and other viruses,
possibly by altering the composition/structure of the cell membrane.
- IFN inhibits primary transcription of many virus genomes e.g. SV40,
HSV.
- Inhibits cell transformation by retroviruses.
Role of interferon (IFN- gamma) in immune regulation:
- In the presence of IL-12 and IFN-gamma, Th0 cells will differentiate
into Th1 cells.
- Stimulates T cytotoxic lymphocytes, neutrophils and NK cells.
- Inhibits the proliferation of Th2 cells
- Blocks the effect of IL-4 on proliferating B-cells.
- Prevents class-switching.
- Activates macrophages to kill phagocytosed microbes (its previous
name was Macrophage Activating Factor)
- Stimulates expression of MHC II and MHC I antigens as well as
co-stimulators on antigen presenting cells.
Application of interferons:
- Interferon is used to treat chronic active hepatitis by HBV, HCV and
Condylomata accuminata (Genital warts) by Human papilloma virus.
- Patients suffering from Hairy cell leukaemia and Kaposi's sarcoma
may benefit from interferon treatment.
Interferon is not thought
to be very effective and may itself produce fever and
vomiting.
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