evolution of (thinking about) dual use research

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.