Multiple Sphingolipid-metabolizing Enzymes Modulate Influenza Virus Replication

Overview

Journal Virology

Specialty Microbiology

Date 2025 Jan 4

PMID 39754863

Authors

Savannah McKenna

Kwang Il Jung

Jennifer J Wolf

Young-Jin Seo

Bumsuk Hahm

Affiliations

Soon will be listed here.

Abstract

The sphingolipid network is sustained principally by the balance of bioactive sphingolipid molecules and their regulation by sphingolipid-metabolizing enzymes. The components in the lipid system display key functions in numerous cellular and disease conditions including virus infections. During the COVID-19 pandemic, there was a fruitful effort to use an inhibitor that blocks the activity of sphingosine kinase (SphK) 2 to cure the devastating disease. Support for the inhibitor came from pre-clinical research on influenza where the inhibitor demonstrated effective protection of mice from influenza-induced morbidity and mortality. This highlights the importance of basic and translational research on the sphingolipid system for improving human health. Multiple sphingolipid-metabolizing enzymes have been reported to regulate influenza virus replication and propagation. In this review, the emphasis is placed on the roles of these enzymes that impact influenza virus life cycle and the conceivable mechanisms for the interplay between influenza virus and the sphingolipid pathway.

References

Smith C, Maines L, Keller S, Ben-Yair V, Fathi R, Plasse T . Recent Progress in the Development of Opaganib for the Treatment of Covid-19. Drug Des Devel Ther. 2022; 16:2199-2211. PMC: 9288228. DOI: 10.2147/DDDT.S367612. View

Yang B, Yao D, Ohuchi M, Ide M, Yano M, Okumura Y . Ambroxol suppresses influenza-virus proliferation in the mouse airway by increasing antiviral factor levels. Eur Respir J. 2002; 19(5):952-8. DOI: 10.1183/09031936.02.00253302. View

Bartke N, Hannun Y . Bioactive sphingolipids: metabolism and function. J Lipid Res. 2008; 50 Suppl:S91-6. PMC: 2674734. DOI: 10.1194/jlr.R800080-JLR200. View

Serra M, Saba J . Sphingosine 1-phosphate lyase, a key regulator of sphingosine 1-phosphate signaling and function. Adv Enzyme Regul. 2009; 50(1):349-62. PMC: 2862839. DOI: 10.1016/j.advenzreg.2009.10.024. View

Marfia G, Navone S, Guarnaccia L, Campanella R, Mondoni M, Locatelli M . Decreased serum level of sphingosine-1-phosphate: a novel predictor of clinical severity in COVID-19. EMBO Mol Med. 2020; 13(1):e13424. PMC: 7744841. DOI: 10.15252/emmm.202013424. View

Parashuraman S, DAngelo G . Visualizing sphingolipid biosynthesis in cells. Chem Phys Lipids. 2018; 218:103-111. DOI: 10.1016/j.chemphyslip.2018.11.003. View

Samuelson A, Carr C, Ruvkun G . Gene activities that mediate increased life span of C. elegans insulin-like signaling mutants. Genes Dev. 2007; 21(22):2976-94. PMC: 2049198. DOI: 10.1101/gad.1588907. View

Edwards M, Becker K, Gripp B, Hoffmann M, Keitsch S, Wilker B . Sphingosine prevents binding of SARS-CoV-2 spike to its cellular receptor ACE2. J Biol Chem. 2020; 295(45):15174-15182. PMC: 7650243. DOI: 10.1074/jbc.RA120.015249. View

Zhu J, Chiang C, Gack M . Viral evasion of the interferon response at a glance. J Cell Sci. 2023; 136(12). PMC: 10411950. DOI: 10.1242/jcs.260682. View

10.

Maceyka M, Sankala H, Hait N, Le Stunff H, Liu H, Toman R . SphK1 and SphK2, sphingosine kinase isoenzymes with opposing functions in sphingolipid metabolism. J Biol Chem. 2005; 280(44):37118-29. DOI: 10.1074/jbc.M502207200. View

11.

Liu H, Sugiura M, Nava V, Edsall L, Kono K, Poulton S . Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform. J Biol Chem. 2000; 275(26):19513-20. DOI: 10.1074/jbc.M002759200. View

12.

Green C, Maceyka M, Cowart L, Spiegel S . Sphingolipids in metabolic disease: The good, the bad, and the unknown. Cell Metab. 2021; 33(7):1293-1306. PMC: 8269961. DOI: 10.1016/j.cmet.2021.06.006. View

13.

Okazaki T, Bielawska A, Domae N, Bell R, Hannun Y . Characteristics and partial purification of a novel cytosolic, magnesium-independent, neutral sphingomyelinase activated in the early signal transduction of 1 alpha,25-dihydroxyvitamin D3-induced HL-60 cell differentiation. J Biol Chem. 1994; 269(6):4070-7. View

14.

Tafesse F, Huitema K, Hermansson M, van der Poel S, van den Dikkenberg J, Uphoff A . Both sphingomyelin synthases SMS1 and SMS2 are required for sphingomyelin homeostasis and growth in human HeLa cells. J Biol Chem. 2007; 282(24):17537-47. DOI: 10.1074/jbc.M702423200. View

15.

Putri W, Muscatello D, Stockwell M, Newall A . Economic burden of seasonal influenza in the United States. Vaccine. 2018; 36(27):3960-3966. DOI: 10.1016/j.vaccine.2018.05.057. View

16.

Du Y, Yang F, Wang Q, Xu N, Xie Y, Chen S . Influenza a virus antagonizes type I and type II interferon responses via SOCS1-dependent ubiquitination and degradation of JAK1. Virol J. 2020; 17(1):74. PMC: 7291424. DOI: 10.1186/s12985-020-01348-4. View

17.

Drews K, Calgi M, Harrison W, Drews C, Costa-Pinheiro P, Shaw J . Glucosylceramide synthase maintains influenza virus entry and infection. PLoS One. 2020; 15(2):e0228735. PMC: 7006932. DOI: 10.1371/journal.pone.0228735. View

18.

Tafesse F, Sanyal S, Ashour J, Guimaraes C, Hermansson M, Somerharju P . Intact sphingomyelin biosynthetic pathway is essential for intracellular transport of influenza virus glycoproteins. Proc Natl Acad Sci U S A. 2013; 110(16):6406-11. PMC: 3631694. DOI: 10.1073/pnas.1219909110. View

19.

French K, Zhuang Y, Maines L, Gao P, Wang W, Beljanski V . Pharmacology and antitumor activity of ABC294640, a selective inhibitor of sphingosine kinase-2. J Pharmacol Exp Ther. 2010; 333(1):129-39. PMC: 2846016. DOI: 10.1124/jpet.109.163444. View

20.

Spiegel S, Milstien S . The outs and the ins of sphingosine-1-phosphate in immunity. Nat Rev Immunol. 2011; 11(6):403-15. PMC: 3368251. DOI: 10.1038/nri2974. View