INTERFERONS , STRUCTURE ,PRODUCTION IN BACTERIA, FUNGI, VIRUS,METHODS FOR PRODUCTION, MECHANISM OF PRODUCTION, GENE COMPOSITION,TYPES OF INTERFERONS
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PRODUCTION OF INTERFERONS M.MEENAKSHI , ASSISTANT PROFESSOR, DEPARTMENT OF MICROBIOLOGY , SRI RAMAKRISHNA COLLEGE OF ARTS & SCIENCE FOR WOMEN, COIMBATORE
Interferons
Interferons
In Bacteria
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.
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
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
Production in vaccina virus
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
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
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 l As 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