Hepatitis B virus upregulates host expression of a-1,2-mannosidases via the PPARa pathway

Hu, Song; Jiang, Li-Bin; Zou, Xiao-Jing; Yi, Wei; Tian, De-Ying

Most enveloped viruses, including HBV, contain envelope protein polysaccharides, which are extensively glycosylated [20] . Protein glycosylation has multiple functions, and sometimes assists in evading immune surveillance [21] . Viruses use the host cell glycosylation system to synthesize and modify their envelope proteoglycans, and thus, the structures of viral envelope glycoproteins can be affected by the glycosylation mechanisms in the host [22] . Indeed, previous studies have shown that applying low-doses of glucosidase inhibitors to host cells changes the phenotype of the viral envelope proteins [23] . This, in turn, can reduce viral infection and affect the virus assembly and/or particle release [23] . For example, the α-glucosidase inhibitor NB-DNJ was previously shown to prevent the HBV from correct folding and the release of viral envelope molecules, and thus, could dose-dependently reduce the virus level [9] . On the other hand, while the α-mannosidase I inhibitor the expression of α-1, 2-mannosidases, we measured the expression of MAN1A1, MAN1A2, MAN1B1, and MAN1C1 in hepatoma cells with or without HBV transfection. MAN1A1, MANA2, MAN1B1, and MAN1C1 protein levels in the HepG2.2.15 and N10 cell lines with stable HBV-transfection were higher than in HepG2 cells (Figure 1 ). To confirm whether HBV infection was the cause of the upregulation, AD38 cells, which express the HBV genome under the control of a tetracycline (Tet)-off promoter, were further investigated. The expression of HBV genes in the AD38 cell line was restricted in the presence of Tet. When Tet was absent, these cells produced 3.5 kb HBV pregenomic RNA and secreted virus-like particles into the supernatant. We found that α-1,2-mannosidase expression in the AD38 cells without Tet was higher than in cells with Tet ( Figure 1A and B) .