Sphingosine‐1‐phosphate related signalling pathways manipulating virus replication

Abstract

Viruses can create a unique cellular environment that facilitates replication and transmission. Sphingosine kinases (SphKs) produce sphingosine‐1‐phosphate (S1P), a bioactive sphingolipid molecule that performs both physiological and pathological effects primarily by activating a subgroup of the endothelial differentiation gene family of G‐protein coupled cell surface receptors known as S1P receptors (S1PR1‐5). A growing body of evidence indicates that the SphK/S1P axis is crucial for regulating cellular activities in virus infections like respiratory viruses, enteroviruses, hepatitis viruses, herpes viruses, and arboviruses replicate. Depending on the type of virus, pro‐ or anti‐viral activities of the SphK/S1P axis sometimes rely on the host immune system and sometimes directly through intracellular signalling pathways or cell proliferation. Recent research has shown novel roles of S1P and SphK in viral replication. Sphingosine kinase isoforms (SphK1 and SphK2) levels can be manipulated by several viruses to promote the effects that are expected. Regulation of cellular signalling pathways plays a significant role in the mechanism. The purpose of this review is to provide insight of the characters played by the SphK/S1P axis throughout diverse viral infection processes. We then assess potential therapeutic methods that are based on S1P signalling and metabolism during viral infections.

Ceramide kinase-mediated C1P metabolism attenuates acute liver injury by inhibiting the interaction between KEAP1 and NRF2

“…Our findings also revealed that SPHK1 and SGPP2, the main enzymes that generated and degraded S1P, were both highly expressed during acute liver injury. Similarly, numerous studies have demonstrated that S1P plays a role in the regeneration and inflammation associated with various liver injuries, such as hepatic ischemia‒reperfusion 43 , liver fibrosis 44 , and hepatitis 45 . For instance, in a study on carbon tetrachloride-induced acute liver injury, SPHK1 mRNA expression and activity increased at 72 h, and S1P facilitated hepatic wound healing through S1PR2 46 , which suggested that S1P plays a role in liver regeneration following acute injury.…”

Serum metabolomics analysis of patients with chronic obstructive pulmonary disease and ‘frequent exacerbator’ phenotype

“…Respiratory infections are common triggers of AECOPD. The SphK/S1P axis has been reported to regulate the host immune system and to exert pro- or anti-viral effects in different types of viral infections by interfering with intracellular signaling pathways ( 56 , 57 ). For example, S1P can enhance endothelial barrier function and epithelial cell survival during respiratory syncytial virus infection by activating the Akt/ERK signaling pathway ( 58 , 59 ).…”

The role of sphingosine-1-phosphate in autophagy and related disorders

“…Besides, intracellular S1P can serve as a second messenger and bind to intracellular targets. For example, S1P can bind with prohibitin-2 (PHB2) to affect mitochondrial respiration in the mitochondria [ 27 ] and combine with histone deacetylases to influence gene expression in the nucleus [ 28 ].…”