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GBP5 is an interferon-induced inhibitor of respiratory syncytial virus.
- Source :
-
Journal of Virology . 2020, Vol. 94 Issue 21, p1-45. 45p. - Publication Year :
- 2020
-
Abstract
- Guanylate binding protein 5 (GBP5) belongs to the guanosine triphosphatase (GTPase) subfamily, which is mainly induced by interferon γ (IFN-γ) and is involved in many important cellular processes, including inflammasome activation and innate immunity against a wide variety of microbial pathogens. However, it is unknown whether GBP5 inhibits respiratory syncytial virus (RSV) infection. Here, we identified GBP5 as an effector of the anti-RSV activity of IFN-γ and found that in children, the weaker immune response, especially the weaker IFN-γ response and the decreased GBP5 expression, leads to RSV susceptibility. Furthermore, we revealed that GBP5 reduced the cell-associated levels of the RSV small hydrophobic (SH) protein, which was identified as a viroporin. In contrast, overexpression of the SH protein rescued RSV replication in the presence of GBP5. The GBP5-induced decrease in intracellular SH protein levels is because GBP5 promotes the release of the SH protein into the cell culture. Moreover, the GBP5 C583A mutants at the C-terminus or lacking the C-terminus region, which impair GBP5 localisation in the Golgi, could not inhibit RSV infection, whereas the GTPase-defective GBP5 maintained RSV inhibition, suggesting that Golgi localisation but not the GTPase activity of GBP5 is required for RSV inhibition. Interestingly, we found that RSV infection or RSV G protein downregulates GBP5 expression by upregulating DZIP3, an E3 ligase, which induces GBP5 degradation through the K48-ubiquitination and proteasomal pathways. Thus, this study reveals a complicated interplay between host restrictive factor GBP5 and RSV infection and provides important information for understanding the pathogenesis of the RSV. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 0022538X
- Volume :
- 94
- Issue :
- 21
- Database :
- Academic Search Index
- Journal :
- Journal of Virology
- Publication Type :
- Academic Journal
- Accession number :
- 146502017
- Full Text :
- https://doi.org/10.1128/JVI.01407-20