In vivo inhibition of influenza A virus replication by RNA interference targeting the PB2 subunit via intratracheal delivery
Journal
PLoS ONE
Journal Volume
12
Journal Issue
4
Pages
e0174523
Date Issued
2017
Author(s)
Huang D.T.-N.
Wang J.-Y.
Chang Y.-H.
Lai M.-J.
Chi Y.-H.
Abstract
Background Influenza virus infection is a major threat to human health. Small interfering RNA (siRNA) is a promising approach for the prevention and treatment of viral infections. In this study, we constructed a series of DNA vector-based short hairpin RNAs (shRNAs) that target various genes of the influenza A virus using the polymerase III U6-RNA promoter to prevent influenza virus infection in vitro and in a mouse model. Results Three sets of DNA vector-based shRNA, two targeting genes encoding the polymerase acidic protein (PA) and one targeting polymerase basic protein 2 (PB2), efficiently inhibited the replication of influenza virus A/WSN/33(H1N1) in vitro. We also successfully prevented influenza virus A/WSN/33(H1N1) infection in a C57BL/6 mouse model by intratracheal delivery of anti-PB2 shRNA. Conclusions Our findings suggest that the PB2-targeting shRNA plasmid showed potential for use as an RNAi-based therapeutic for influenza virus infection. ? 2017 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
SDGs
Other Subjects
short hairpin RNA; unclassified drug; viral protein; virus polymerase acidic protein; virus polymerase basic protein 2; PB2 protein, Influenzavirus A; RNA directed RNA polymerase; small interfering RNA; animal cell; animal experiment; animal model; animal tissue; Article; controlled study; disease model; DNA vector; drug targeting; female; gene targeting; in vitro study; in vivo study; influenza A (H1N1); Influenza A virus; Influenza A virus (H1N1); MDCK cell line; mouse; nonhuman; protein expression; RNA interference; virus inhibition; virus replication; animal; C57BL mouse; drug effects; endotracheal intubation; genetics; Influenza A virus; Orthomyxoviridae Infections; physiology; procedures; RNA interference; RNAi therapeutics; virus replication; Animals; Female; Influenza A virus; Intubation, Intratracheal; Mice; Mice, Inbred C57BL; Orthomyxoviridae Infections; RNA Interference; RNA Replicase; RNA, Small Interfering; RNAi Therapeutics; Viral Proteins; Virus Replication
Publisher
Public Library of Science
Type
journal article