Within-host Spatial Dynamics of Viruses and Defective Interfering Particles
✍ Scribed by STEVEN A FRANK
- Publisher
- Elsevier Science
- Year
- 2000
- Tongue
- English
- Weight
- 205 KB
- Volume
- 206
- Category
- Article
- ISSN
- 0022-5193
No coin nor oath required. For personal study only.
✦ Synopsis
Defective-interfering (DI) viruses arise spontaneously by deletion mutations. The shortened genomes of the DI particles cannot replicate unless they coinfect a cell with a wild-type virus. Upon coinfection, the DI genome replicates more quickly and outcompetes the wild type. The coinfected cell produces mostly DI viruses. At the population level, the abundances of DI and wild-type viruses #uctuate dramatically under some conditions. In other cases, 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 models have shown that either #uctuation or persistence can occur for plausible parameter values. I develop new mathematical models for the population dynamics of DI and wild-type viruses. My work extends the theory by developing speci"c predictions that can be tested in the laboratory. These predictions, if borne out by experiment, will explain the key processes that control the diversity of observed outcomes. The most interesting prediction concerns the rate at which killed host cells are replaced. A low rate of replacement causes powerful epidemics followed by a crash in viral abundance. As the rate of replacement increases, the frequency of oscillations increases in DI and wild-type viral abundances, but the severity (amplitude) of the #uctuations declines. At higher replacement rates for host cells, nearly all cells become infected by DI particles and a low level of #uctuating, wild-type viremia persists.