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PLoS Genet. 2016 May 5;12(5):e1005986. doi: 10.1371/journal.pgen.1005986. eCollection 2016 May.

Exploiting Genetic Interference for Antiviral Therapy.

Author information

1
Gladstone Institutes (Virology and Immunology), San Francisco, California, United States of America.
2
Department of Genetics, Stanford University School of Medicine, Stanford, California, United States of America.
3
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, United States of America.

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.

PMID:
27149616
PMCID:
PMC4858160
DOI:
10.1371/journal.pgen.1005986
[Indexed for MEDLINE]
Free PMC Article

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