Introduction to Virology Lecture 3: Viral Replication Cycle PDF

Introduction to Microbiology: Virology Lecture 3 – Viral replication cycle Darryn Knobel BVSc MSc PhD [email protected] Viral replication cycle Virus essentials Viruses are obligate intracellular parasites The production of new infectious particles (virions) can take place only within a cell (o...

Introduction to Microbiology: Virology Lecture 3 – Viral replication cycle Darryn Knobel BVSc MSc PhD [email protected] Viral replication cycle Virus essentials Viruses are obligate intracellular parasites The production of new infectious particles (virions) can take place only within a cell (one that is susceptible and permissive to infection) Viral reproduction requires many different functions of host cells: machinery for translation of viral mRNAs sources of energy enzymes for genome replication Viral replication cycle Steps in the replication cycle 1. 2. 3. 4. 5. 6. Attachment and entry mRNA synthesis Translation Genome replication Assembly Release (Virologists divide the replication cycle into these steps to faciliate study and understanding, but no such artificial boundaries occur) Attachment and entry mRNA synthesis Translation Genome replication Assembly Release Viral replication cycle Definitions A susceptible cell produces the receptor(s) required for viral entry A susceptible cell may or may not be able to support viral replication A resistant cell does not produce the required receptors A resistant cell may or may not be able to support viral replication A permissive cell is able to support viral replication when a viral genome is introduced A permissive cell may or may not be susceptible A susceptible AND permissive cell is the only cell that can take up a viral particle and replicate it Viral replication cycle: Attachment and entry Viral replication cycle: Attachment and entry Attachment and entry Virus particles are too large to diffuse across the plasma membrane 3 steps: 1. Adhere to cell surface (no specificity) 2. Attach to specific receptor molecules on cell surface (more than one receptor type may be involved) 3. Transfer genome inside the cell Receptors have cell functions – viruses have evolved to be able to bind to them Section heading Slide title Viral replication cycle: Attachment and entry Receptor-binding sites for attachment Non-enveloped viruses: one or more viral capsid proteins Attachment via surface features (canyons and loops) Attachment via protruding fibers Poliovirus Adenovirus Enveloped viruses: glycoproteins incorporated into the cell-derived membranes of virus particles Mediate fusion with new host cell membrane Influenza virus Coronavirus Section heading Slide title Viral replication cycle: Attachment and entry Entry into host cell Cells use different mechanisms for the uptake of macromolecules from the extracellular fluid After binding to receptors, virus particles may gain entry into cells though these mechanisms Viral replication cycle: Attachment and entry Entry into host cell: enveloped viruses Fusion with plasma membrane Fusion with endosomal membrane Viral replication cycle: Attachment and entry Entry into host cell: enveloped viruses https://youtube.com/clip/UgkxkbTCetKrKFxmbcCt_Q5kiD6_wStvFbTU?si=tsqcLoVVId6uNPWP Viral replication cycle: Attachment and entry Entry into host cell: non-enveloped viruses Disrupting the endosomal membrane (adenovirus) Forming a pore in the endosomal membrane (poliovirus) Disrupting the lysosomal membrane (reovirus) Viral replication cycle: Attachment and entry Entry into host cell: bacteriophages Viral replication cycle: mRNA synthesis, translation and genome replication Viral replication cycle: mRNA synthesis, translation and genome replication Baltimore classification of viral genomes Viral replication cycle: mRNA synthesis, translation and genome replication DNA genomes I VII II Viral replication cycle: mRNA synthesis, translation and genome replication RNA genomes IV III VI V Viral replication cycle: mRNA synthesis, translation and genome replication Nucleic Acid Polymerases An enzyme that synthesizes long chains (polymers) of nucleic acids Produced by Template Product Name Host cells Most DNA viruses DNA DNA DNA-dependent DNA polymerase (DdDp) Host cells Some DNA viruses (poxviruses) DNA RNA DNA-dependent RNA polymerase (DdRp) Some RNA viruses (retroviruses) Some DNA viruses (hepadnaviridae) RNA DNA RNA-dependent DNA polymerase (=reverse transcriptase/RT) Other RNA viruses RNA RNA RNA-dependent RNA polymerase (RdRp) Viral replication cycle: mRNA synthesis, translation and genome replication DNA genomes I DdRp (cellular except pox) DdDp (cellular/viral) VII DNA repair DdRp (cellular) II DdRp DdDp (cellular) RT DdDp Viral replication cycle: mRNA synthesis, translation and genome replication RNA genomes IV ss(-) RNA and dsRNA viruses: Viral RNA-dependent RNA polymerases are packaged in the virion along with the genome and carry out both mRNA synthesis and replication of the genome RdRp V III RdRp RdRp RdRp RdRp RdRp VI RT RT RT Viral replication cycle: mRNA synthesis, translation and genome replication Site of mRNA synthesis Viral replication cycle: Assembly and release Viral replication cycle: Assembly and release Viral replication cycle: Assembly and release Assembly Viral replication cycle: Assembly and release Acquisition of an envelope Viral replication cycle: Assembly and release Assembly at internal membranes Viral replication cycle: Assembly and release Assembly at internal membranes: examples Coronavirus Herpesvirus Viral replication cycle: Assembly and release Release Three different mechanisms: Budding Exocytosis Cell lysis Enveloped viruses: budding or exocytosis Nonenveloped viruses: lysis (generally – some exceptions) Viral replication cycle: Retroviruses Viral replication cycle: Retroviruses Retroviruses