Host-directed combinatorial RNAi improves inhibition of diverse strains of influenza A virus in human respiratory epithelial cells.

Autor: Estrin MA; Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America., Hussein ITM; Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America., Puryear WB; Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America., Kuan AC; Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America., Artim SC; Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America., Runstadler JA; Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2018 May 18; Vol. 13 (5), pp. e0197246. Date of Electronic Publication: 2018 May 18 (Print Publication: 2018).
DOI: 10.1371/journal.pone.0197246
Abstrakt: Influenza A virus infections are important causes of morbidity and mortality worldwide, and currently available prevention and treatment methods are suboptimal. In recent years, genome-wide investigations have revealed numerous host factors that are required for influenza to successfully complete its life cycle. However, only a select, small number of influenza strains were evaluated using this platform, and there was considerable variation in the genes identified across different investigations. In an effort to develop a universally efficacious therapeutic strategy with limited potential for the emergence of resistance, this study was performed to investigate the effect of combinatorial RNA interference (RNAi) on inhibiting the replication of diverse influenza A virus subtypes and strains. Candidate genes were selected for targeting based on the results of multiple previous independent genome-wide studies. The effect of single and combinatorial RNAi on the replication of 12 diverse influenza A viruses, including three strains isolated from birds and one strain isolated from seals, was then evaluated in primary normal human bronchial epithelial cells. After excluding overly toxic siRNA, two siRNA combinations were identified that reduced mean viral replication by greater than 79 percent in all mammalian strains, and greater than 68 percent in all avian strains. Host-directed combinatorial RNAi effectively prevents growth of a broad range of influenza virus strains in vitro, and is a potential therapeutic candidate for further development and future in vivo studies.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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