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Lecture 5

BIOL442 - Lecture 5 - (+) RNA.pdf

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University of Waterloo
BIOL 442
Christine Dupont

Set 5RNACytoplasmic TransportSome viruses require movement to nucleus for transcription Some like Picornaviridae carry out transcription in the cytoplasmTo get to the nucleus interaction with cytoskeletal transport machinery microtubules or microfilaments is required2 modes either by vesicle endosome movement or by freed subviral particle partially uncoatedEg rabies virusUninfected neuron transport of vesicles containing messenger molecules occurs along microtubules up to the cell body of the neuronInfected neurons rabies virus hitches a ride on this transport system to reach CNS including the brainCan move 8 to 20 mm per day along axonsTime that clinical signs appear is shorter in the young and when bites are close to CNS head neckIn CNS virus has easy access to any tissue infiltrated by neurons including salivary glands and tear ductsViruses bud out from neurons in these glands into the secretionsRabiesinduced aggressive biting behavior and hypersalivation in the host animal maximizes chance of viral infection of a new hostDynein action molecular motor transport systemIf needs to get into nucleus from hereNuclear localization signals NLS target capsid to nucleus NLS first discovered in SV40A small sequence of amino acids 20 aa embedded in a peptideUsually consists largely of basic aa arginine lysineNLS are recognized by cytoplasmic receptor proteins called importinsImportins attach to NLS on proteins and dock them to the nuclear poreHere nuclear pore complex brings in the peptides and nucelic acidComplex is an elaborate collection of proteins that form a discrete structure at the nuclear membrane maintaining a controlled pore across which large molecules such as peptides and nucelic acids pass with the assistance of various carrier proteins Normally transport of nucleic acid RNA is one way nucleuscytoplasmNuclear transport proteins do thisTo get nucleic acid cytoplasmnucleus protein seems to usually be associated with it at nuclear pore actual transport mechanism is not well worked out for most virusesViral mRNA productionsTranslationReplicationCentral dogma reviewEukaryotesDNARNAProteinHost cell is set up to do this so if virus wants to hijack cell mechanisms for this then must present itself in a compatible fashionSimplest waydsDNA viruses enter nucleus and use all host machineries for transcription translation replicationEG Circoviridaereptiles amphibians Polyomaviridae Parvoviridaeis ssDNA but uses host DNA polymerase to make it into dsDNA in nucleus BUTTo use host cell replication enzymes DNA polymerase must wait unit cell enters S phase when these become availableNot a good replication strategy as many host cells dont divide G0Better to bring your own polymerase with you andor encode itTranscriptiontranslation produces active viral polymerase unlinked to cell cycleOrInduce entry into S phase eg Polymoaviridae AdenoviridaeThe RNA viruses VertebratesDiverseStructureNaked and enveloped virusesNaked viruses are all icosahedral Reo Brina Calici Picorna New Section 1 Page 1
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