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Unformatted text preview: uses Negative Sense Influenza Genome RNA Segments as Template Unprimed RNA Synthesis - PA, PB1 and PB2 function as a trimeric Replicase Complex • PB1 -- in the Presence of increased Levels of NP -- acts as an RNA Polymerase (“Unprimed RNA Synthesis”) The Functions of PA and PB2 during Replication are Unknown. - PB1 “Reads Through” the short Poly-U Tract • So PB1 polymerizes a full-length Copy of the Genome - Readthrough requires the Presence of NP. - Resultant Positive Sense cRNA Molecule serves as Template • PB1 -- in the Presence of NP -- again acts as an RNA Polymerase - Resultant Negative Sense RNA Molecules are Genome - Each Genomic RNA is assembled into a Nucleocapsid • Nucleocapsids associate with M 1 and NS 2- NS 2 serves as a Nuclear Export Signal Influenza Page 8 Influenza Virus Assembly • HA, NA and M 2 form Patches in the Host Cell Membrane - HA, NA and M 2 Patches exclude Host Cell Membrane Proteins - NA digests Host Cell Sialic Acid Residues in the Membrane Selective Nucleocapsid Incorporation Model • Eight (8) Nucleocapsids associate prior to Budding - Each Virus Particle will contain the complete Genome • Viral Proteins recognize and interact sequentially with specific Signal Sequences on 5´ and 3´ Ends of Genome RNA - These Signal Sequences may control -- • Individual Nucleocapsid Recruitment • Nucleocapsid-to-Nucleocapsid Associations - Seven (7) Nucleocapsids are arranged in a Cylinder • The Eighth is inside the Cylinder The Evidence is largely from Electron Microscopy. While the Images are enticing, Electron Microscopy is notorious for generating Artifacts. Random Nucleocapsid Incorporation Model • Approximately 11 Nucleocapsids are randomly incorporated during Budding - Only 10% of Virus Particles will contain the complete Genome Randomly packaging about 11 Nucleocapsids into each Virus Particle would work well enough and save the Virus the Trouble of having to deal with a complex Packaging Scheme. This would also explain why it takes more than one Influenza Virus to initiate an Infection. Influenza Virus Budding • M 1 attached to Nucleocapsids interacts with Cytoplasmic Tails of HA in the Host Cell Membrane - As Nucleocapsids bind to more HA ʼ s, the Virus buds from the Host Cell, swiping some Host Cell Membrane for its Envelope • The Influenza Virus Particle buds from the Host Cell - NA reverses HA-Binding to Sialic Acid and digests Mucous so the Virus Particle can get out from underneath the Mucous NA Inhibitors interfere with the Release of Influenza Virus Particles...
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- Spring '09
- influenza virus, Influenza Page