Defective interfering particles: effects in modulating virus growth and persistence.

Defective interfering virus particles (DIP) frequently play an important part in viral persistence in vitro, and may in some instances modify a virus infection in vivo, causing attenuation or persistence of the infection. To explain certain aspects of the growth of these mutants in vitro, other factors have been invoked such as interferon, mutations in the wild-type virus or the infected cells, or other substances released by infected cells that attenuate the infection. We present here a simple model of the growth of DIP in vitro which shows that (a) the observed population dynamics of DIP can readily be explained without invoking such extrinsic factors; (b) the initial multiplicity of infection of DIP is the principal determinant of the outcome of infection in both single- and repeated-passage cultures; and (c) in a long-term culture in vitro, the criterion used to decide the time of virus passage directly determines how long the standard virus, DIP, and cells survive. This model may be used with minor modifications to predict the behavior in vitro of other mutant viruses with a dominantly interfering phenotype.