Analysis of the HIV-1 central polypurine tract

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Analysis of the HIV-1 central polypurine tract in a foamy viral vector background: 

Analysis of the HIV-1 central polypurine tract in a foamy viral vector background University of Würzburg , Institute for Virology and Immunobiology , Würzburg , Germany MD/PhD student Sergey Shityakov 8 th International Foamy Virus Conference Greece, Argos 2010

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(-) strand DNA initiates at the primer binding site When (-) strand elongation passes the polypurine tract (ppt) region, the RNA template escapes digestion by RNase H and serves as a primer for (+) strand synthesis by DNA dependent DNA polymerization (DDDP) Reverse transcription

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cPPT (HIV) vs. cPPT (PFV) GGGCAAGGGAAAGAGG GAGGAGAGGGG

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Reverse transcription J-J Kupiec, P Sonigo, JGV 1996

Aim of the project:: 

Aim of the project: To study the cPPT -CTS (HIV) effects upon the foamy viral replication in order to increase foamy viral vectors infectivity for growth- arrested (G1/S) permissive cells via cPPT modifications.

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PFV and HIV systems Truncated viral backbone Packaging plasmids For PFV system : For negative control : pMD9 (Cas I, II, cPPT ) 1) pMD9 (-ENV) pGAG 2) pcDNA (mock) pPOL pENV For HIV system : pWPXL ( Ψ, Pol, cPPT-CTS ) PsPAX2 (Gag) pMD 2.G (VSV-G, pseudotyping)

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Construction of foamy viral vectors

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Procedure PEI transfection of HEK 293T cells Transduction of human alveolar basal epithelial A549 cells 5μg/ml 5μg/ml

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Transduction rates of A549 cell

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Summary Modified foamy viral vector show a reduction in transduction rates of dividing A549 cells PFV vectors are able to infect G1/S growth-arrested A549 cells but at extremely low titers in comparison to lentiviral vectors. Finally, the HIV cPPT can not be substituted for the PFV cPPT without loss of functionality, probably because the cognate RT enzyme is required for recognition of PPT and CTS sequences.

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Acknowledgments to PD. Dr.Carsten Scheller Axel Rethwilm’s lab: Dr.Tatiana Wiktorowicz Daniel Matthes

Thank you for your attention: 

Thank you for your attention