Evolution of (Thinking About) Dual Use Research
Bert Jacobs, Professor
School of Life Sciences
Poxviridae
Chordopoxvirinae
EntomopoxvirinaeOrthopoxviruses-Smallpox Camelpox
Rabbitpox Mousepox
Cowpox Vaccinia
Monkeypox
Parapoxviruses-ORF virus
Avipoxviruses-Canarypox, fowlpox
Leporipoxviruses-Myxomatosis
Molluscipoxviruses-Molluscum contagiosum
Suipoxviruses-Swinepox
Yatapoxviruses-Yaba tumor virus
InterferonInterferon
1
10
100
-IFN
+IF
N
EMCV
-IFN
+IF
N
VSV
% V
iru
s Y
ield
1
10
100
-IFN
+IF
N
+IF
N/V
V
EMCV
-IFN
+IF
N
+IF
N/V
V
VSV
-IFN
+IF
N
VV
% V
iru
s Y
ield
• 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.
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
Poxviridae
Chordopoxvirinae
EntomopoxvirinaeOrthopoxviruses-Smallpox Camelpox
Rabbitpox Mousepox
Cowpox Vaccinia
Monkeypox
Parapoxviruses-ORF virus
Avipoxviruses-Canarypox, fowlpox
Leporipoxviruses-Myxomatosis
Molluscipoxviruses-Molluscum contagiosum
Suipoxviruses-Swinepox
Yatapoxviruses-Yaba tumor virus
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
Recombinant VACVexpressing ASFV gene
neoR-GFP/PE/LASFV GENE
CourS-RFP
neoR-GFP/PE/LASFV GENE
VACV-E3L MSKIYIDERSDAEIVCAAIKNIGIEGATAAQLTRQLNMEKREVNKALYDLQRSAMVYSSD 60VARV-E3L MSKIYIDERSDAEIVCEAIKNIGLEGVTAVQLTRQLNMEKREVNKALYDLQRSAMVYSSD 60MPXV-F3L -------------------------------------MEKREVNKALYDLQRSTMVYSSD 23 ****************:******
VACV-E3L DIPPRWFMTTEADKPDADAM--ADVIIDDVSREKSMREDHKSFDDVIPAKKIIDWKDANP 118VARV-E3L DIPPRWFMTTEADKPDAMAMTMADAIIDDVSREKSMREDHKSFDDVIPAKKIIDWKNANP 120MPXV-F3L DTPPRWSTTMDADTRPTDSD--ADAIIDDVSREKSMREDNKSFDDVIPVKKIIYWKGVNP 81 * **** * :**. : : **.**************:********.**** **..** VACV-E3L VTIINEYCQITKRDWSFRIESVGPSNSPTFYACVDIDGRVFDKADGKSKRDAKNNAAKLA 178VARV-E3L VTIINEYCQITKRDWSFRIESVGPSNSPTFYACVDIDGRVFDKADGKSKRDAKNNAAKLA 180MPXV-F3L VTVINEYCQITRRDWSFRIESVGPSNSPTFYACVDIDGRVFDKADGKSKRDAKNNAAKLA 141 **:********:************************************************
VACV-E3L VDKLLGYVIIRF 190VARV-E3L VDKLLGYVIIRF 192MPXV-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.