Virus Life Cycle PDF

BMS2037 Cellular microbiology and virology Virus Life Cycle Dr. Marine Petit [email protected] Lecture overview Introduction to virus life cycle Virus entry and uncoating Virus protein translation Genome replication Virus assembly Virus release and transmission Virus replicates inside a ce...

BMS2037 Cellular microbiology and virology Virus Life Cycle Dr. Marine Petit [email protected] Lecture overview Introduction to virus life cycle Virus entry and uncoating Virus protein translation Genome replication Virus assembly Virus release and transmission Virus replicates inside a cell A virus is dependent on its host cell Virus must use same tools as host cell Understanding viruses requires a knowledge of cell biology and molecular biology Animal cell Important info! Viruses do not “grow” Cell growth Virus assembly Inoculation phase: During this phase, the virus undergoes the first step of the viral life cycle: attachment (to host cells). Growth Curve and Life Cycle of Viruses - Wolfram Demonstrations Project Viruses do not “grow” Eclipse: Viruses are now being manufactured within the host cells. This phase include the penetration step where virus enter the cells and the uncoating of the genetic material. Finally, we see the manufacture of the viral components (viral proteins, and new genetic materials) Growth Curve and Life Cycle of Viruses - Wolfram Demonstrations Project Viruses do not “grow” Maturation: After synthesis of capsids, enzymes and other materials, new virus particles (virions) are formed during the assembly step. Total virus count increases before release occurs. Viruses do not grow and divide – they assemble Important info! Growth Curve and Life Cycle of Viruses - Wolfram Demonstrations Project Virus replicates inside a cell A virus is dependent on its host cell Virus must use same tools as host cell Understanding viruses requires a knowledge of cell biology and molecular biology Virology is an integrative science Important info! Viruses hitch a ride on normal cellular processes Endocytosis Cytoskeletal transport Nuclear import/export Transcription machinery Translation machinery Secretory pathway Virus entry & uncoating Virus attachment and entry Glycoproteins on the surface of the virus will recognize attachment and entry receptors to initiate the penetration of the viral particle in the cells. Important info! Example of entry receptors Principle of Virology book Different viruses can bind to same receptors (e.g: Adenovirus and Coxsackievirus B3) Same virus can bind to multiple receptors (e.g: Retroviruses can bind to 16 receptors) Two mode of virus entry Important info! Uncoating Uncoating could happen in the cytoplasm or within the nucleus Is it difficult to penetrate the cytoplasm? The cytoplasm is crowded! Movement of large protein complexes will not occur by diffusion! Hijacking the microtubule network Viralzone.expasy.org Important info! KINESIN MOTOR PROTEIN WITH VESICLE Virus protein translation Central Dogma of Molecular Biology RNA viruses are an exception to this dogma because their molecular biology does not involve DNA All viruses need to make virus proteins The virus will use the host cell translation machinery One well studied viral strategies is the translational shutoff: 1. Virus stop cellular translation 2. Use the translation complex for its own translation Virus protein synthesis Non-Structural proteins Genome Antagonise host replication responses Structural proteins Virus assembly Late Early Protein levels Important info! Diversity of viral proteins Flavivirus polyprotein model Thogotovirus segmented protein model 5-minute break Surrey attendance code: BQ-NJ-BM Genome replication Key fact makes your life easier Viral genomes must make mRNA that can be read by host ribosomes All viruses on the planet follow this rule, no known exception Important info! The seven classes of viral genomes Baltimore classification I. dsDNA II. ssDNA III. dsRNA IV. ss (+) RNA V. ss (-) RNA VI. ss (+) RNA with DNA intermediate VII. dsDNA gapped virus Important info! If you know the genome structure you should be able to deduce: How mRNA is made from the genome How the genome is copied to make more genomes dsDNA virus Replication of the genetic material occurs in the cell Nucleus Herpes simplex viruses DNA dependent RNA polymerase encoded by host cells dsDNA virus Replication of the genetic material occurs in the cell Nucleus Herpes simplex viruses DNA dependent DNA polymerase encoded by host cells Herpes simplex virus pathology dsDNA gapped virus DNA dependent DNA polymerase encoded by host cells Replication of the genetic material occurs in the cell Nucleus dsDNA gapped virus DNA dependent DNA polymerase encoded by host cells Replication of the genetic material occurs in the cell Nucleus fulminant hepatic failure, chronic liver disease and cirrhosis ssDNA virus DNA dependent DNA polymerase encoded by host cells ssDNA virus DNA dependent DNA polymerase encoded by host cells Bombix mori iteradensovirus Ss (+) RNA virus Replication is cytoplasmic only, no DNA form. Mosquito-borne Flaviviruses like Zika virus RNA dependent RNA polymerase encoded by the virus Ss (+) RNA virus Replication is cytoplasmic only, no DNA form. Mosquito-borne Flaviviruses like Zika virus RNA dependent RNA polymerase encoded by the virus Microcephaly in infant infected by Zika virus during pregnancy Brazil epidemic of 2016 Ss (-) RNA virus Replication can be cytoplasmic (Bunyaviruses) OR nuclear (Influenza virus). Influenza virus RNA dependent RNA polymerase encoded by the virus Ss (-) RNA virus Replication can be cytoplasmic (Bunyaviruses) OR nuclear (Influenza virus). Influenza virus RNA dependent RNA polymerase encoded by the virus 1918 Influenza Pandemic 20-30 million deaths. dsRNA virus Replication is cytoplasmic only, no DNA form. RNA dependent RNA polymerase encoded by the virus Retro-virus Replication of the genetic material occurs in the cell Nucleus Reverse Transcriptase RNA dependent DNA polymerase Human immunodeficiency virus HIV HIV pandemic: 34 million infected people and 2.1 million death per year Definitions mRNA (ribosome ready) is always the plus (+) strand DNA of equivalent polarity is also the (+) strand RNA and DNA complements of (+) strands are negative (-) strands Not all (+) RNA is mRNA! Virus assembly Where is viral assembly happening in infected cell? Viruses use membrane to create small viral factories Viralzone.expasy.org Nuclear viral assembly Liu et al., 2015 Viralzone.expasy.org Cytoplasmic viral assembly Viroplasm in cryo-electron microscopy Rotavirus dsRNA genetic material Structure of the capsid Capsid form and assembly 3 capsid forms: Helical Icosahedric Scaffolded icosahedric Capsid assembly: formation of the capsid shell. Packaging: viral genome placement inside a capsid or an envelope. Viralzone.expasy.org Virus release & transmission Virus budding by cellular exocytosis Envelopes of viruses are derived from membrane, could be internal membrane or plasma membrane. Often enveloped viruses use secretory pathway to assemble, mature, and egress the cell. Important info! Virus budding by cellular exocytosis Cellular exocytosis pathway is very popular mainly because it is not disturbing the cell HIV budding off an infected cell HIV Budding Assembly Membrane curvature Envelope protein Formation of lentivirus nucleocapsid linked to budding process Envelope proteins are responsible for directing assembly and budding at that location Membrane fission Maturation Naked virus egress Non-lytic viral egress Lytic viral egress Double-membrane vesicles formed by autophagy Cell lysis: apoptosis, necroptosis Exosomes Viral proteins that induce rupture of the cell membrane (e.g viroporin, poliovirus) Loss of membrane integrity with inhibition of protein synthesis Viral transmission Cell free spreading Through vesicular transport Direct cell-to-cell Paracellular transport through proteic channel Both Important info! Antivirals target can inhibit many steps