In:
PLOS ONE, Public Library of Science (PLoS), Vol. 18, No. 6 ( 2023-6-23), p. e0287545-
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0287545
DOI:
10.1371/journal.pone.0287545.g001
DOI:
10.1371/journal.pone.0287545.g002
DOI:
10.1371/journal.pone.0287545.g003
DOI:
10.1371/journal.pone.0287545.g004
DOI:
10.1371/journal.pone.0287545.g005
DOI:
10.1371/journal.pone.0287545.s001
DOI:
10.1371/journal.pone.0287545.s002
DOI:
10.1371/journal.pone.0287545.s003
DOI:
10.1371/journal.pone.0287545.s004
DOI:
10.1371/journal.pone.0287545.s005
DOI:
10.1371/journal.pone.0287545.s006
DOI:
10.1371/journal.pone.0287545.s007
DOI:
10.1371/journal.pone.0287545.s008
DOI:
10.1371/journal.pone.0287545.s009
DOI:
10.1371/journal.pone.0287545.r001
DOI:
10.1371/journal.pone.0287545.r002
DOI:
10.1371/journal.pone.0287545.r003
DOI:
10.1371/journal.pone.0287545.r004
Sprache:
Englisch
Verlag:
Public Library of Science (PLoS)
Publikationsdatum:
2023
ZDB Id:
2267670-3
