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Journal of Virology, February 2001, p. 1205-1210, Vol. 75, No. 3
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.3.1205-1210.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Expression of Mouse Interleukin-4 by a Recombinant Ectromelia Virus Suppresses Cytolytic Lymphocyte Responses and Overcomes Genetic Resistance to Mousepox

Ronald J. Jackson,1,2,* Alistair J. Ramsay,2,dagger Carina D. Christensen,2 Sandra Beaton,1 Diana F. Hall,1,Dagger and Ian A. Ramshaw2

Pest Animal Control Cooperative Research Centre, CSIRO Sustainable Ecosystems,1 and Division of Immunology and Cell Biology, John Curtin School of Medical Research, Australian National University,2 Canberra, Australia

Received 25 July 2000/Accepted 13 November 2000

Genetic resistance to clinical mousepox (ectromelia virus) varies among inbred laboratory mice and is characterized by an effective natural killer (NK) response and the early onset of a strong CD8+ cytotoxic T-lymphocyte (CTL) response in resistant mice. We have investigated the influence of virus-expressed mouse interleukin-4 (IL-4) on the cell-mediated response during infection. It was observed that expression of IL-4 by a thymidine kinase-positive ectromelia virus suppressed cytolytic responses of NK and CTL and the expression of gamma interferon by the latter. Genetically resistant mice infected with the IL-4-expressing virus developed symptoms of acute mousepox accompanied by high mortality, similar to the disease seen when genetically sensitive mice are infected with the virulent Moscow strain. Strikingly, infection of recently immunized genetically resistant mice with the virus expressing IL-4 also resulted in significant mortality due to fulminant mousepox. These data therefore suggest that virus-encoded IL-4 not only suppresses primary antiviral cell-mediated immune responses but also can inhibit the expression of immune memory responses.

* Corresponding author. Mailing address: CSIRO Sustainable Ecosystems, GPO Box 284, Canberra ACT 2601, Australia. Phone: 61 (02) 6242 1717. Fax: 61 (02) 6242 1511. E-mail: R.Jackson{at}cse.csiro.au.

dagger Present address: Centre for Biomolecular Vaccine Technology, Discipline of Immunology and Microbiology, University of Newcastle, Newcastle, New South Wales, Australia.

Dagger Present address: CSIRO Plant Industry, Canberra ACT, Australia.

Journal of Virology, February 2001, p. 1205-1210, Vol. 75, No. 3
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.3.1205-1210.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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