Infection of hepatitis B virus in extrahepatic endothelial tissues mediated by endothelial progenitor cells.
BACKGROUND
Hepatitis 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.


RESULTS
In 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.


CONCLUSIONS
These 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.
Rong
Qifei
Q
Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, People's Republic of China. rongqifei@126.com
Huang
Jun
J
Su
Enben
E
Li
Jun
J
Li
Jianyong
J
Zhang
Lili
L
Cao
Kejiang
K
D000818:Animals; D002478:Cells, Cultured; D004279:DNA, Viral / Q000096:biosynthesis; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000821:virology*; D006321:Heart / Q000821:virology; D006509:Hepatitis B / Q000150:complications*; D006512:Hepatitis B Core Antigens / Q000096:biosynthesis; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis; D006515:Hepatitis B virus / Q000254:growth & development*; D006801:Humans; D007231:Infant, Newborn; D007511:Ischemia; D007668:Kidney / Q000821:virology; D008168:Lung / Q000821:virology; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009203:Myocardial Infarction; D013234:Stem Cells / Q000821:virology*; D019737:Transplants; D014771:Virion / Q000648:ultrastructure
D004279:DNA, Viral; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens