11 - retro - notes II.docx

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University of Toronto St. George
Molecular Genetics and Microbiology
Alan Cochrane

MGY378 – Feb3 Meristic acid causes it to be inserted into lower side of plasma membrane – Meristic acid and matrix protein – C-type virus – forms C-type indentation when released from cell Other retroviruses called B and D type viruses – form capsid in cytoplasm – icosahedral cores form in cytoplasm, travel to membrane, then bud off - C type do not see viral assembly on viral membrane - Need to mature before beomcing infectious o Because polyprotein need to be cleaved down to be infectious - Protease is self-activating - Activate protease prior to release step – catastrophic to virus – lose all enzymes o Through gag part of molecule Reasons why a cell cannot support replication of a specific retrovirus? - Two steps determine cell replicates virus o If virus can get in  If receptor for virus is present or not o If virus enters but must be in right environment, as determined by promoter  If cell type is wrong and has wrong transcription factors, cannot read promoter of virus  Some viruses inuce sarcomas, others leukemias, and other work in other places of body – going after specific tissue of body o Virus does not provide transcription factors, polymerase – all belonging to host  Host determines whether virus replicates or not Assembly - tRNA primer has to come into particle and be positioned on RNA during assembly process - pulling in genomic RNA and tRNA into particle to assemble something to have genome and primer - psi = packaging signal sitting at three prime of five prime splice site – splicing out packaging signal recognized by NC portion of gag protein – called zinc knuckles because it’s an abbreviated zinc finger - NC binds to psi sequence in unspliced RNA – drags in RNA into particle - tRNA involves gag pol protein – drags in tRNA to serve as primer and positions it on the RNA to sit there ready to prime when hit nucleotide pool - assembled complete particle – surface unit – Pseudotypes - change the envelope protein on surface of virus – through virus called pseudotyping – two viruses infecting cell - FelvA and B enter same cell, integrate both their genomes, express both genomes, assemble o Because two viruses share same packaging signal – mixture of viral particles produced when bud off o Pseudotyping  Often have both envelope proteins on same particle  But can convert back to original specificity because only encode for one envelope if take this psueodtype and infect another cell  Each genome encodes for one envelope  Genome is not always the same as what is expressed on the surface/envelope o Ex. HIV hit only cD4 positive T cell – canspeudotype the virus so change type of cell virus infects  Redirect to infect cells in brain, liver, etc.  Useful in gene therapy To increase coy number - Virus just want survive by amplification of its genome - By two ways - Horizontal amplification o Generation of new virus to infect naive cells - Vertical amplification o Causing infected cell to divide Retroviral transformation - Retroviruses transform cells o Can induce cancer - Rapid onset and predictable onset of tumours - Origin is polyclonal - Extra reading frame – Src o Protein encoded by Src also found in all human cells o Virus induces tumour by expressing oncogene in cell – every cell that receives the virus will express the oncogene - so regardless where virus integrates into genome
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