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Evolution of (Thinking About) Dual Use Research. Bert Jacobs, Professor School of Life Sciences. Orthopoxviruses-Smallpox Camelpox Rabbitpox Mousepox Cowpox Vaccinia Monkeypox.
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Evolution of (Thinking About) Dual Use Research Bert Jacobs, Professor School of Life Sciences
Orthopoxviruses-Smallpox Camelpox Rabbitpox Mousepox Cowpox Vaccinia Monkeypox Entomopoxvirinae Poxviridae Leporipoxviruses-Myxomatosis Chordopoxvirinae Yatapoxviruses-Yaba tumor virus Suipoxviruses-Swinepox Parapoxviruses-ORF virus Molluscipoxviruses-Molluscum contagiosum Avipoxviruses-Canarypox, fowlpox
100 10 1 EMCV VSV % Virus Yield -IFN -IFN +IFN +IFN
100 10 1 EMCV VSV VV % Virus Yield -IFN -IFN -IFN +IFN +IFN +IFN +IFN/VV +IFN/VV
Poxviruses • Large dsDNA viruses (130,000-370,000 bp). • Brick-shaped; 140-260 nm in diameter; 220-450 nm long. • Replicate entirely in the cytoplasm of infected cells. • Encode immune evasion genes. • Easy to insert genes into and delete genes from poxviruses.
JOURNAL OF VIROLOGY, Feb. 2001, p. 1205–1210 Vol. 75, No. 3 Expression of Mouse Interleukin-4 by a Recombinant Ectromelia Virus Suppresses Cytolytic Lymphocyte Responses and Overcomes Genetic Resistance to Mousepox Ronald J. Jackson, Alistair J. Ramsay, Carina D. Christensen, Sandra Beaton, Diana F. Hall, And Ian A. Ramshaw
Orthopoxviruses-Smallpox Camelpox Rabbitpox Mousepox Cowpox Vaccinia Monkeypox Entomopoxvirinae Poxviridae Leporipoxviruses-Myxomatosis Chordopoxvirinae Yatapoxviruses-Yaba tumor virus Suipoxviruses-Swinepox Parapoxviruses-ORF virus Molluscipoxviruses-Molluscum contagiosum Avipoxviruses-Canarypox, fowlpox
Trends in ImmunologyVolume 26, Issue 6, June 2005, Pages 339-345 The ‘supervirus’? Lessons from IL-4-expressing poxviruses Marianne M. Stanford and Grant McFadden
JOURNAL OF VIROLOGY, Feb. 2001, p. 1205–1210 Vol. 75, No. 3 Expression of Mouse Interleukin-4 by a Recombinant Ectromelia Virus Suppresses Cytolytic Lymphocyte Responses and Overcomes Genetic Resistance to Mousepox Ronald J. Jackson, Alistair J. Ramsay, Carina D. Christensen, Sandra Beaton, Diana F. Hall, And Ian A. Ramshaw
viral DNA CourS-RFP neoR-GFP/PE/LASFV GENE Recombinant VACV expressing ASFV gene neoR-GFP/PE/LASFV GENE
VACV-E3L MSKIYIDERSDAEIVCAAIKNIGIEGATAAQLTRQLNMEKREVNKALYDLQRSAMVYSSD 60 VARV-E3L MSKIYIDERSDAEIVCEAIKNIGLEGVTAVQLTRQLNMEKREVNKALYDLQRSAMVYSSD 60 MPXV-F3L -------------------------------------MEKREVNKALYDLQRSTMVYSSD 23 ****************:****** VACV-E3L DIPPRWFMTTEADKPDADAM--ADVIIDDVSREKSMREDHKSFDDVIPAKKIIDWKDANP 118 VARV-E3L DIPPRWFMTTEADKPDAMAMTMADAIIDDVSREKSMREDHKSFDDVIPAKKIIDWKNANP 120 MPXV-F3L DTPPRWSTTMDADTRPTDSD--ADAIIDDVSREKSMREDNKSFDDVIPVKKIIYWKGVNP 81 * **** * :**. : : **.**************:********.**** **..** VACV-E3L VTIINEYCQITKRDWSFRIESVGPSNSPTFYACVDIDGRVFDKADGKSKRDAKNNAAKLA 178 VARV-E3L VTIINEYCQITKRDWSFRIESVGPSNSPTFYACVDIDGRVFDKADGKSKRDAKNNAAKLA 180 MPXV-F3L VTVINEYCQITRRDWSFRIESVGPSNSPTFYACVDIDGRVFDKADGKSKRDAKNNAAKLA 141 **:********:************************************************ VACV-E3L VDKLLGYVIIRF 190 VARV-E3L VDKLLGYVIIRF 192 MPXV-F3L VDKLLSYVIIRF 153 *****.******
Lessons Learned? • Depending on the circumstances, seemingly innocuous research can have potential dual use implications. • Difficult to know where research will lead us, it is important to consider the potential consequences of the research we do as we are doing it and as we are publishing it.