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Virus Replication Process
- 1. REPLICATION OF VIRUSES BY DR JAWAD NAZIR ASSISTANT PROFESSOR DEPARTMENT OF MICROBIOLOGY UNIVERSITY OF VETERINARY AND ANIMAL SCIENCES, LAHOREUNIVERSITY OF VETERINARY AND ANIMAL SCIENCES, LAHORE
- 2. Virus replication? p Process by which viruses y multiply inside the host cells by using the cellular machinery to produce the progeny virionsproduce the progeny virions Replication of viruses
- 3. Events in the replicationp Eclipse phaseEclipse phase Interval between the viral penetration and appearance of the first progeny virionsappearance of the first progeny virions Duration of replication cycle ranges from 6‐40 hourshours Replication of viruses
- 4. Steps in the replicationp p AttachmentAttachment Entry/penetration UncoatingUncoating Transcription T l tiTranslation Replication of viral genome Assembly Release Replication of viruses
- 6. Attachment First step to initiate infectionFirst step to initiate infection Receptor ligand interaction Ligand on virus surfaceLigand on virus surface Host cell receptors This virus‐cell interaction determines the host range and tissue tropism of the viruses Viruses might have more than one ligand and may g g y bind to various cell receptors in sequential order Replication of viruses
- 7. Attachment Initial viral attachment to cells is through a fewInitial viral attachment to cells is through a few receptors Weak Reversible When attachment to sufficient receptors Strong Irreversible Replication of viruses
- 11. Attachment of influenza viruses Hemagglutinin molecules Sialic acid receptors Replication of viruses
- 14. Entry/Penetrationy/ All animal viruses must cross the plasmaAll animal viruses must cross the plasma membrane of the cells Some viruses must cross the nuclear envelop,Some viruses must cross the nuclear envelop, usually via nuclear pore Replication of viruses
- 15. Mechanisms of virus entryy Receptor mediated endocytosisReceptor mediated endocytosis Clathrin coated pits Acidification within vesicles results into degradation of viral structures Fusion with membrane of endosome Fusion with plasma membrane proteins Translocation of genome into cytoplasm through h l h l bchannels in the plasma membranes Replication of viruses
- 21. Fusion with plasma membraneFusion with plasma membrane Replication of viruses
- 25. Uncoating g Purpose of uncoating is to release the viral genomep g g In non‐enveloped viruses uncoating proceeds to completion In enveloped viruses transcription starts before complete uncoating is achieved Uncoating may occurUncoating may occur At plasma membrane while penetrating Within endosomeWithin endosome In cytoplasm At nuclear membrane Replication of viruses At nuclear membrane
- 27. Transcription and translationp TranscriptionTranscription The process of synthesis of complementary RNA (usually mRNA) strand from a DNA or RNA(usually mRNA) strand from a DNA or RNA template TranslationTranslation Process by which genetic information present on mRNA directs the synthesis of proteins from aminomRNA directs the synthesis of proteins from amino acids Replication of viruses
- 28. Enzymes involved in virus replicationy p Cellular enzymes DNA dependent DNA polymerase Synthesizes DNA from DNA DNA dependent RNA l ( ) Synthesizes RNA from DNA polymerase (Transcriptase) y Viral enzymes DNA dependent DNA l Synthesizes DNA from DNA polymerase y DNA dependent RNA polymerase (Transcriptase) Synthesizes RNA from DNA RNA dependent RNARNA dependent RNA polymerase Synthesizes RNA from RNA RNA dependent DNA polymerase (Reverse‐ Synthesizes DNA from RNA Replication of viruses transcriptase)
- 30. Central dogma of molecular biology g gy The flow of genetic information is always from DNA to RNA and thenThe flow of genetic information is always from DNA to RNA and then to protein, with genetic information transmitted from one generation to the next through copying from DNA to DNA Replication of viruses
- 33. Transcriptionp The viruses that replicate in nucleus uses cellularThe viruses that replicate in nucleus uses cellular enzymes while the ones that replicate in cytoplasm encode their own All viruses that carry out transcription in the cytoplasm (except the plus strand RNA viruses) havecytoplasm (except the plus‐strand RNA viruses) have the transcriptases packed in the virion Replication of viruses
- 36. Need to make mRNA PLUS (POSITIVE) SENSE RNA GENOMES AAA (+ve) sense mRNA Replication of viruses 36
- 37. Need to make mRNA MINUS (NEGATIVE) SENSE RNA GENOMES RNA polymerase must beRNA polymerase must be packaged in virion. AAA (+ve) sense mRNA (‐ve) sense genomic RNA Replication of viruses 37
- 40. RNA viruses that do NOT have a DNA phase Genome RNA-dependent Infectivity of Initial event in RNA viruses that do NOT have a DNA phase Genome RNA dependent RNA polymerase (=transcriptase) IN VIRION Infectivity of RNA Initial event in cell Plus-stranded RNA No Infectious Translation Negative- stranded RNA Yes Non-infectious Transcription Double- stranded RNA Yes Non-infectious Transcription Replication of viruses 40
- 41. RETROVIRUSESRETROVIRUSES Genome RNA-dependent DNA polymerase (=reverse Infectivity of RNA Initial event in cell (=reverse transcriptase) in virion Plus-stranded RNA Yes Non- infectious Reverse transcription Replication of viruses 41
- 45. Types of transcription and translation Early transcription and translation:Early transcription and translation: Virus enzymes required for TranscriptionTranscription Shut down of cellular function Late transcription and translation:Late transcription and translation: Structural proteins Virus associated enzymesVirus associated enzymes Replication of viruses
- 46. Categories of proteins encoded by the viruses Structural proteins of viruses S uc u a p o e s o uses Virus associated enzymes (transcriptases) Non structural proteins mainly enzymes required for transcription, replication of NA and cleavage Regulatory proteins that control the temporal expression of viral genome Proteins down regulating the expression of cellular genome Replication of viruses
- 47. Categories of proteins encoded by the viruses Oncogene products (Oncoproteins) and inactivators of O coge e p oduc s (O cop o e s) a d ac a o s o cellular tumor suppressors Proteins influencing viral virulence host range tissueProteins influencing viral virulence, host range, tissue tropism etc Virokines, act on noninfected cells to modulate the progress of infection in the host Replication of viruses
- 50. Assembly and maturation y I h d lIcosahedral symmetry Replication of viruses
- 51. Assembly and packing y p g I h d l N l idIcosahedral Nucleocapsid Replication of viruses
- 52. Assembly and packing y p g I h d lIcosahedral Nucleocapsid Replication of viruses
- 53. Assembly and packing y p g H li l N l idHelical Nucleocapsid Replication of viruses
- 54. Virus release mechanism BuddingBudding Enveloped viruses are released by budding from plasma memberane Cell Lysis Naked viruses are released by lysis y y Exocytosis Viruses may acquire envelope by budding through y q p y g g membranes of Golgi apparatus or rough endoplasmic reticulum Replication of viruses