Abstract
Chronic hepatitis B Virus (HBV) infection has high morbidity, high pathogenicity and unclear pathogenesis. To elucidate the relationship between HBV replication and host phospholipid metabolites, we measured 10 classes of phospholipids in serum of HBV infected patients and cells using ultra performance liquid chromatograph-triple quadruple mass spectrometry. We found that the levels of phosphatidylcholine (PC), phosphatidylethanolamine, and lyso-phosphatidic acid were increased in HBsAg (+) serum of infected patients compared with HBsAg (−), while phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, and sphingomyelin were decreased, which were confirmed in an HBV infected HepG2.2.15 cell line. We further evaluated the enzyme levels of PC pathways and found that PCYT1A and LPP1 for PC synthesis were up-regulated after HBV infection. Moreover, HBV replication was inhibited when PCYT1A and LPP1 were inhibited. These results indicated that the PC synthesis in HBV infected host are regulated by PCYT1A and LPP1, which suggests that PCYT1A, LPP1 could be new potential targets for HBV treatment.
Highlights
Hepatitis B Virus (HBV) is a double stranded DNA virus and belongs to hepadnavirdae family
The total levels of PC and lyso-phosphatidic acid (LPA) increased while the total levels of SM decreased in hepatitis B surface antigen (HBsAg)(+) group comparing to the HBsAg (−) group (Fig. 1B)
The total levels of 23 phospholipid species were significantly changed in HBsAg (+) group comparing to the HBsAg (−) group (Fig. 1C)
Summary
Hepatitis B Virus (HBV) is a double stranded DNA virus and belongs to hepadnavirdae family. We found that stimulated phosphatidylcholine via choline kinase alpha (CHKA) is associated with HBV infection and inhibiting CHKA can suppress HBV replication[11]. This suggests that phospholipids could play an important role in HBV replication. Huang et al identified a set of chronic hepatitis B (CHB)-associated biomarkers including lyso-phosphatidylcholines, phosphatidylcholines, phosphatidylinositol, phosphatidylserine in CHB patients[20]. These reports emphasized important roles of phospholipids in HBV infection. Our investigation provided more information furthering the understanding of the pathogenesis and potential new targets of HBV treatment
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