Within-host spatial dynamics of viruses and defective interfering particles

Defective-interfering (DI) viruses arise spontaneously by deletion mutation s. The shortened genomes of the DI particles cannot replicate unless they c oinfect a cell with a wild-type virus. Upon coinfection, the DI genome repl icates more quickly and outcompetes the wild type. The coinfected cell prod uces mostly DI viruses. At the population level, the abundances of DI and w ild-type viruses fluctuate dramatically under some conditions. In other cas es, the DI viruses appear to mediate persistent infections with relatively low levels of host cell death. This moderation of viral damage has led some to suggest DI particles as therapeutic agents. Previous mathematical model s have shown that either fluctuation or persistence can occur for plausible parameter values. I develop new mathematical models for the population dyn amics of DI and wild-type viruses. My work extends the theory by developing specific predictions that can be tested in the laboratory. These predictio ns, if borne out by experiment, will explain the key processes that control the diversity of observed outcomes. The most interesting prediction concer ns the rate at which killed host cells are replaced. A low rate of replacem ent causes powerful epidemics followed by a crash in viral abundance. As th e rate of replacement increases, the frequency of oscillations increases in DI and wild-type viral abundances, but the severity (amplitude) of the flu ctuations declines. At higher replacement rates for host cells, nearly all cells become infected by DI particles and a low level of fluctuating, wild- type viremia persists. (C) 2000 Academic Press.