Defective Deletion Mutant Amplification

Defective deletion mutants can be replicated in superinfected cells by parasitism of the intact virusʹ replication machinery, and through replication with the host cell. We show by analysis of a mathematical model that dynamic stability of superinfected cell growth is crucial in determining the frequency of deletion mutant infected cells, i.e. there is a critical infectivity threshold ρscbelow which the density of proliferative virus is significantly reduced by the presence of defective deletion mutants. Above ρsc, proliferative virus principally occurs as superinfected cells (wild type with defective deletion mutant). The thresholdρsc , and the interference effects of the deletion mutant, increase with deletion mutant parasitism of the wild-type replication machinery in superinfected cells. The interaction of virally infected cells with host homeostasis determines whether immune escape by deletion mutant infected cells is necessary for the interference window to exist. Only when the deletion mutant has a detrimental effect on infected host cell replication did we observe periodic behaviour.