5. PRODUCTION OF INTERFERONS:
Interferons are produced by living animal cells, both in vivo as well as
cultured cells.
Interferon production and its antiviral activity require expression of cellular
genes, and these functions are blocked by inhibitors of transcription and
translation.
Thus, virus-infected host cells fail to produce interferon in presence of
actinomycin D, an inhibitor of eukaryotic RNA polymerase.
When the inhibitor is added after 2 hr of infection, interferon production
is not inhibited, suggesting that transcription is completed by that time.
6. PROCESS OF INTERFERON
PRODUCTION
Interferon production starts after initiation of viral maturation and
continues for 20 to 50 hr after that.
Then the production stops, due to formation of a repressor which
presumably is formed or activated only when the interferon concentration
in the producing cell exceeds a certain threshold concentration.
Most of the interferon is transported from the producing cell to other
neighbouring cells
7. Process…..
The substance in a virus that is responsible for interferon synthesis by the
host cell is known as interferon inducer.
The nature of this substance was identified by Merigan (1970) as double-
stranded RNA.
The activity seems to reside in polyribonucleotide’s with a high helical
content.
The double- stranded RNA viruses — like reoviruses — can act as
interferon inducer without replication.
Single- stranded RNA viruses can act as inducers only after replication
when they form double-stranded replicative intermediates. DNA-viruses
can also induce interferons, presumably due to overlapping transcription
of viral DNA as observed in case of vaccinia virus
9. Production in Fungi
Fungal viruses which have mostly double-stranded RNA genomes are also
efficient inducers of interferons.
Some synthetic polymers containing riboinosinic acid, ribocytidylic acid
(Poly I: C) as well as those containing riboadenylic acid and ribouridylic
acid (Poly A: U) are also good inducers.
All interferon inducers are characterized by high molecular weight, high
density of anionic groups and resistance to enzymatic degradation.
DNA and DNA-RNA hybrids have been found to be ineffective as
interferon inducers
10. Structure of Interferons
The induction of interferon synthesis concerns α- and β-interferon’s which
belong to a single class, called Type I.
Gamma-interferon belongs to a separate class, called Type II.
The human Υ-interferon is the single representative of its type. The gene
coding the y-interferon protein is located on the long arm of chromosome
12.
The gene has three introns, while the genes of α- and β- interferons are
without any introns.
Gamma-interferon (human) has 146 amino acids and is an N-glycosylated
tetrameric protein. It is induced by antigenic stimulation of T-lymphocytes
11. Mechanism of production
In presence of the inducer which is viral ds-RNA, the α- and β-interferon
genes of the host chromosome(s) are activated to produce interferon m-
RNAs.
Those are then translated intoα- and β- interferon proteins.
These proteins at first accumulate in the producing cell and eventually lAs
the interferon concentration in the producing cell rises above a threshold
level, it activates another gene of the producing cell which codes for a
repressor protein which feeds back and stops further synthesis of interferon.
As a result, virus-infected cells generally produce only small quantities of
interferons.
The interferon molecules that leave the producing cell reach the
neighbouring uninfected host cells and interact with the cell membrane or
nuclear membrane receptors of these cells. Thereby these cells are induced
to synthesise antiviral proteins. These antiviral proteins are the actual agents
that provides protection to these host cells against viral infection