Federation of American Scientists Case Studies in Dual Use Biological Research Module 4.0: Mousepox Case Study
Topic: "Mousepox" Experiment Subtopic: Mousepox Experiment: Encoding IL-4 Gene

Dr. Jackson of the Commonwealth Scientific and Industrial Research Organisation (CSIRO) and Dr. Ramshaw of the Australian National University collaborated on an experiment that employed recombinant Ectromelia virus (ECTV) to introduce the mouse egg shell protein zona pellucida 3 (ZP3) into female mice promoting an immune response that would lead to sterility. The hypothesis was that by infecting mice with the genetically altered virus that normally causes mousepox, the mice would contract an attenuated case of the disease and present an immune response to the virus that would extend to the mouse egg protein. This extended immune response would lead to anti-ZP3 antibodies attacking the mouse’s own eggs, causing sterility.

When it became apparent that production of antibodies against the mouse egg cells was adequate in some mouse strains, but not in more resistant ones, they decided to try to boost antibody production by using an engineered recombinant mousepox virus. The altered virus, ECTV-IL(TK+), was produced by transfection of the pFB-TK-IL4 plasmid encoding interleukin-4 protein (IL-4) into wild type mousepox virus. IL-4 is one of a family of cytokine regulators (a Type 2 cytokine which influences the development of a T-Helper-2 response), which plays a pivotal role in the delay-type hypersensitivity response. Previous research in other systems suggested that a virus expressing IL-4 would increase the antibody-producing response in mice while mitigating the effect of virus-clearing cells (T-helper cells). While Ramshaw and Jackson understood that there was a possibility of a lethal immunosuppressant virus, they believed that the genetic resistance of the mice would be strong enough to withstand systemic effects.

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