title: Exploiting Genetic Interference for Antiviral Therapy.
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.
authors.affiliation: Gladstone Institutes (Virology and Immunology), San Francisco, California, United States of America.
authors.forename: Elizabeth J
authors.identifier: 0000-0001-9445-6620
authors.initials: EJ
authors.lastname: Tanner
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America.
authors.forename: Karla A
authors.initials: KA
authors.lastname: Kirkegaard
authors.affiliation: Gladstone Institutes (Virology and Immunology), San Francisco, California, United States of America.|Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, United States of America.
authors.forename: Leor S
authors.initials: LS
authors.lastname: Weinberger
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D024882:Drug Resistance, Viral / Q000235:genetics*; D029043:Ebolavirus / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D014644:Genetic Variation; D016679:Genome, Viral; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000235:genetics* / Q000472:pathogenicity; D012641:Selection, Genetic / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
chemical_list: D000998:Antiviral Agents