Open AccessIn vivo inhibition of influenza A virus replication by RNA interference targeting the PB2 subunit via intratracheal delivery
Author(s) -
Daniel Tsung-Ning Huang,
Chi-Jen Lu,
Pei-Lan Shao,
LuanYin Chang,
JinYuan Wang,
Yi-Hsuan Chang,
Ming Kuen Lai,
YaHui Chi,
LiMin Huang
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0174523
Subject(s) - virology , small hairpin rna , virus , rna interference , influenza a virus , polymerase , biology , viral replication , small interfering rna , rna polymerase , rna , gene , microbiology and biotechnology , genetics
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.