Abstract
Rapidly evolving viruses are a major threat to human health. Such
viruses are often highly pathogenic (e. g., influenza virus, HIV, Ebola
virus) and routinely circumvent therapeutic intervention through
mutational escape. Error-prone genome replication generates
heterogeneous viral populations that rapidly adapt to new selection
pressures, leading to resistance that emerges with treatment. However,
population heterogeneity bears a cost: when multiple viral variants
replicate within a cell, they can potentially interfere with each other,
lowering viral fitness. This genetic interference can be exploited for
antiviral strategies, either by taking advantage of a virus's inherent
genetic diversity or through generating de novo interference by
engineering a competing genome. Here, we discuss two such antiviral
strategies, dominant drug targeting and therapeutic interfering
particles. Both strategies harness the power of genetic interference to
surmount two particularly vexing obstacles-the evolution of drug
resistance and targeting therapy to high-risk populations-both of which
impede treatment in resource-poor settings.
