| RRC ID |
76680
|
| 著者 |
Masaya Fukushi, Ryosuke Ohsawa, Yasushi Okinaka, Daisuke Oikawa, Tohru Kiyono, Masaya Moriwaki, Takashi Irie, Kosuke Oda, Yasuhiro Kamei, Fuminori Tokunaga, Yusuke Sotomaru, Hirofumi Maruyama, Hideshi Kawakami, Takemasa Sakaguchi
|
| タイトル |
Optineurin deficiency impairs autophagy to cause interferon beta overproduction and increased survival of mice following viral infection
|
| ジャーナル |
PLOS ONE
|
| Abstract |
Background
Optineurin (OPTN) is associated with several human diseases, including amyotrophic lateral sclerosis (ALS), and is involved in various cellular processes, including autophagy. Optineurin regulates the expression of interferon beta (IFNβ), which plays a central role in the innate immune response to viral infection. However, the role of optineurin in response to viral infection has not been fully clarified. It is known that optineurin-deficient cells produce more IFNβ than wild-type cells following viral infection. In this study, we investigate the reasons for, and effects of, IFNβ overproduction during optineurin deficiency both in vitro and in vivo.
Methods
To investigate the mechanism of IFNβ overproduction, viral nucleic acids in infected cells were quantified by RT-qPCR and the autophagic activity of optineurin-deficient cells was determined to understand the basis for the intracellular accumulation of viral nucleic acids. Moreover, viral infection experiments using optineurin-disrupted (Optn-KO) animals were performed with several viruses.
Results
IFNβ overproduction following viral infection was observed not only in several types of optineurin-deficient cell lines but also in Optn-KO mice and human ALS patient cells carrying mutations in OPTN. IFNβ overproduction in Optn-KO cells was revealed to be caused by excessive accumulation of viral nucleic acids, which was a consequence of reduced autophagic activity caused by the loss of optineurin. Additionally, IFNβ overproduction in Optn-KO mice suppressed viral proliferation, resulting in increased mouse survival following viral challenge.
Conclusion
Our findings indicate that the combination of optineurin deficiency and viral infection leads to IFNβ overproduction in vitro and in vivo. The effects of optineurin deficiency are elicited by viral infection, therefore, viral infection may be implicated in the development of optineurin-related diseases.
|
| 巻・号 |
18
|
| ページ |
e0287545
|
| 公開日 |
2023-6-23
|
| DOI |
10.1371/journal.pone.0287545
|
| 解説 |
TILLING
|
| PMID |
37352136
|
| PMC |
PMC10289332
|
| MeSH |
Amyotrophic Lateral Sclerosis* / genetics
Animals
Autophagy / genetics
Cell Cycle Proteins* / genetics
Humans
Immunity, Innate
Interferon-beta / genetics
Membrane Transport Proteins* / genetics
Mice
Mice, Knockout
Transcription Factor TFIIIA / genetics
Transcription Factor TFIIIA / metabolism
Virus Diseases*
|
| IF |
2.74
|
| リソース情報 |
| メダカ |
OK-Cab (MT830) |
