IMR Press / FBL / Volume 24 / Issue 4 / DOI: 10.2741/4752

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
IFN-Alpha1 antisense RNA represses human influenza A virus growth in a guinea pig system
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1 Laboratory of Microbiology and Cell Biology, Department of Pharmacy, College of Pharmaceutical Sciences, Ritsumeikan University, Kusatsu, Shiga, Japan
2 Material Business Division, Hosokawa Micron Corporation, Hirakata, Osaka, Japan
*Correspondence: kimurato@ph.ritsumei.ac.jp (Tominori Kimura)
Front. Biosci. (Landmark Ed) 2019, 24(4), 798–818; https://doi.org/10.2741/4752
Published: 1 March 2019
(This article belongs to the Special Issue Regulatory long non-coding RNA)
Abstract

We reported a natural antisense (AS) long non-coding RNA as an important modulator of interferon-Alpha1 (IFNA1) mRNA levels. We showed that IFN-Alpha1 AS promotes IFNA1 mRNA stability by transient duplex formation and inhibition of miR-1270-induced mRNA decay. Here, we performed a proof-of-concept experiment to verify that the AS-mRNA regulatory axis exerts in vivo control of innate immunity. We established a model system for influenza virus infection using guinea pig, which encodes a functional MX1 gene for the type I IFN pathway. This system allowed us to investigate the effects of antisense oligoribonucleotides representing functional domains of guinea pig IFN-Alpha1 AS on gpIFNA1 mRNA levels and, consequently, on viral proliferation in the respiratory tract of influenza virus-infected animals. We demonstrated that pulmonary-administered asORNs inhibited the proliferation of the virus in the animals by modulating IFNA1 mRNA levels. These results indicate that, in light of the proposed actions, asORNs may modulate the level of IFNA1 mRNA in vivo, indicating that IFN-Alpha1 AS plays a pivotal role in determining the outcome of type I IFN responses.

Keywords
lncRNA
Interferon
Alpha
IFN
Influenza A
Virus
Guinea pig
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