Recombinant vaccinia viruses that express the human or mouse IL-2 gene are rapidly eliminated from immunoincompetent nude mice whereas control viruses cause lethal infections. To understand the role that virus-encoded IL-2 plays in attenuation, we investigated the mechanism of virus elimination from nude mice. Survival correlated with accelerated clearance of the virus. Treatment of infected mice with antibodies to eliminate NK cells or to neutralize interferon-γ suggested that both are involved in the elimination of IL-2-producing virus. However, lytic activity of NK cells was not necessary as shown by studies with beige mice. Coinfection with IL-2-expressing and control virus resulted in lethal infection of nude mice, indicating the absence of significant systemic immunity. Focally acting immunopotentiating and chemotactic activities of virus-encoded IL-2 and host-derived interferon-γ seem to confer protection in this novel approach to virus attenuation.
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