Xu M, Xia S, Wang M, Liu X, Li X, Chen W, Wang Y,. Enzymatic independent role of sphingosine kinase 2 in regulating the expression of type I interferon during influenza A virus infection. PLoS Pathog. 2022 Sep 7;18(9):e1010794
Influenza virus has the ability to circumvent host innate immune system through regulating certain host factors for its effective propagation. However, the detailed mechanism is still not fully understood. Here, we report that a host sphingolipid metabolism-related factor, sphingosine kinase 2 (SPHK2), upregulated during influenza A virus (IAV) infection, promotes IAV infection in an enzymatic independent manner. The enhancement of the virus replication is not abolished in the catalytic-incompetent SPHK2 (G212E) overexpressing cells. Intriguingly, the sphingosine-1-phosphate (S1P) related factor HDAC1 also plays a crucial role in SPHK2-mediated IAV infection. We found that SPHK2 cannot facilitate IAV infection in HDAC1 deficient cells. More importantly, SPHK2 overexpression diminishes the IFN-β promoter activity upon IAV infection, resulting in the suppression of type I IFN signaling. Furthermore, ChIP-qPCR assay revealed that SPHK2 interacts with IFN-β promoter through the binding of demethylase TET3, but not with the other promoters regulated by TET3, such as TGF-β1 and IL6 promoters. The specific regulation of SPHK2 on IFN-β promoter through TET3 can in turn recruit HDAC1 to the IFN-β promoter, enhancing the deacetylation of IFN-β promoter, therefore leading to the inhibition of IFN-β transcription. These findings reveal an enzymatic independent mechanism on host SPHK2, which associates with TET3 and HDAC1 to negatively regulate type I IFN expression and thus facilitates IAV propagation.
See Also:
Latest articles in those days:
- Generation of Nasal Cell-Derived Human Alveolar Organoids and Organoid-Macrophage Assembloids for in Vitro Lung Modeling 15 hours ago
- Determinants of the Seasonal Influenza Vaccination Uptake Among People Aged 50 Years or Above During and After the Pandemic: A Systematic Review 1 days ago
- [preprint]A GIS-based framework for standardized environmental characterization in One-Health surveillance: a case study of HPAI monitoring in wetlands 1 days ago
- First detection and transatlantic introduction of Influenza A(H3N2) subclade K (J.2.4.1) into Ecuador: insights from genomic sentinel surveillance 1 days ago
- Assessment of influenza virus and coronavirus tropism, replication competence and disease severity in ex vivo and in vitro cultures of the human respiratory tract 2 days ago
[Go Top] [Close Window]


