Abstract
BackgroundHepatitis B virus (HBV) replication has been reported to be involved in many extrahepatic viral disorders; however, the mechanism by which HBV is trans-infected into extrahepatic tissues such as HBV associated myocarditis remains largely unknown.ResultsIn this study, we showed that human cord blood endothelial progenitor cells (EPCs), but not human umbilical vein endothelial cells (HUVECs) could be effectively infected by uptake of HBV in vitro. Exposure of EPCs with HBV resulted in HBV DNA and viral particles were detected in EPCs at day 3 after HBV challenge, which were peaked around day 7 and declined in 3 weeks. Consistently, HBV envelope surface and core antigens were first detected in EPCs at day 3 after virus challenge and were retained to be detectable for 3 weeks. In contrast, HBV covalently closed circular DNA was not detected in EPCs at any time after virus challenge. Intravenous transplantation of HBV-treated EPCs into myocardial infarction and acute renal ischemia mouse model resulted in incorporation of HBV into injured heart, lung, and renal capillary endothelial tissues.ConclusionThese results strongly support that EPCs serve as virus carrier mediating HBV trans-infection into the injured endothelial tissues. The findings might provide a novel mechanism for HBV-associated myocarditis and other HBV-related extrahepatic diseases as well.
Highlights
Hepatitis B virus (HBV) replication has been reported to be involved in many extrahepatic viral disorders; the mechanism by which HBV is trans-infected into extrahepatic tissues such as HBV associated myocarditis remains largely unknown
Our results suggest that the harboring of HBV in endothelial progenitor cells (EPCs) could serve as one of extrahepatic infective sources, which might point to a novel role of EPCs in mediating HBV associated myocarditis and other HBV-related extrahepatic diseases as well
Immunohistochemistry showed that the cells were positive for endothelial cell surface markers such as von Willebrand factor (vWF) and CD31 expression (Fig. 1C and 1D)
Summary
Hepatitis B virus (HBV) replication has been reported to be involved in many extrahepatic viral disorders; the mechanism by which HBV is trans-infected into extrahepatic tissues such as HBV associated myocarditis remains largely unknown. As many as 20% of patients with hepatitis B virus (HBV) infection experience a spectrum of extrahepatic disorders that includes dermatologic disease, polyarthralgias and arthritis, glomerulonephritis, polymyositis, aplastic anemia, neuropathy, vasculitis and myocarditis [1,2,3]. Recent studies revealed that the virus has extensive reservoirs of extrahepatic replication [4]. In contrast, several other studies have demonstrated that the HBV is not replicated in peripheral blood mononuclear cells (PBMCs) [13], endothelial cells [14], and lymphatic tissues [15]. Whether HBV could be replicated in extrahepatic tissues remains controversial
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