Production of defective interfering virus in the brains of mice by an avirulent, in contrast with a virulent, strain of Semliki forest virus

Abstract

An avirulent strain (A7) of Semliki Forest virus formed nearly as much haemagglutinating and complement fixing antigen in the brains of adult mice as a virulent (V13) strain, yet the infectivities of the brain tissues were different by about 100-fold. It appeared therefore that defective virus particles were fomed by A7 but these were not demonstrated by fluorescent antibody studies. In short-term organ cultures of adult mouse brain, A7 derived from mouse brain showed a typical interference pattern in inoculum infectivity response curves. Furthermore, when mixed suspensions of brain-grown V13 and A7 with equal infectivities were inoculated the inoculum infectivity response patterns showed significant depressions of the V13 response at higher inocula. Such interference was not detected if chick cell grown A7 and V13 were substituted for the mouse grown virus. The avirulence of A7 in adult mice and its rapid protective effect against lethal V13 infection could be due to the production of defective interfering virus particles in the brain.