Identification of NTCP in human podocytes and its mediating effect on the direct HBV infection of kidney tissue

Abstract Background: Direct hepatitis B virus (HBV) infection in kidney tissue is associated with glomerulonephritis. However, it is unclear how HBV enters into kidney cells, We investigated the expression of sodium taurocholate cotransporting polypeptide (NTCP), an entry-specific receptor of HBV, in human renal podocytes and explored the ability of NTCP to mediate HBV-infected podocytes. Methods: We detected the expression of NTCP in the renal tissue of patients with HBV and in cultured human podocytes using immunocytochemical and immunofluorescence co-localization along with western blotting. Human podocytes cultured in vitro were infected with HBV-containing supernatant derived from HepG2.2.15 cells. HBsAg, HBeAg, HBV DNA, HBV CCC DNA, and HBcAg in the podocytes were detected by ELISA, RT-PCR, and immunofluorescence. Results: NTCP was expressed in the kidney podocytes of patients and in human renal podocytes cultured in vivo. HBsAg, HBeAg, HBV DNA, HBV CCC DNA, and HBcAg were expressed in cultured human podocytes with HBV-containing supernatant. Knocking down NTCP with shRNA attenuated the HBV infection in the cultured podocytes with HBV-containing supernatant.Up-regulateing NTCP with WT-NTCP enhanced HBV infection in the cultured podocytes with HBV-containing supernatant. Conclusions: NTCP is expressed in human renal podocytes, where it mediates HBV infection. The findings provide a theoretical bases and a potential target (NTCP) for preventing the direct infection of podocytes by HBV.