Endothelial progenitor cell mediates transport of hepatitis B.
BACKGROUND
Hepatitis B virus (HBV) replication has been reported to be involved in many extrahepatic viral disorders; however, the mechanism by which HBV is transinfected into extrahepatic tissues such as myocardium and causes HBV associated myocarditis remains largely unknown.


METHODS
In this study, endothelial progenitor cells (EPCs) were infected by HBV and then transfused into ischemic model of mice. HBV surface and core antigen as well as mutation of HBV particles were detected by immunohistochemistry, fluorescent activated cell sorter and transmission electron microscopy in vitro and in vivo.


RESULTS
Human cord blood EPCs, but not human umbilical vein endothelial cells (HUVECs) could be effectively infected by taking up HBV in vitro. HBV envelope surface and core antigen expressions were first detectable in EPCs at day 3 after virus challenge, sustained for up to 11 days, and decreased thereafter. Similarly, the virus particles were the most abundant in EPCs in the first week observed by a transmission electron microscope, and declined in 3 weeks after HBV infection. HBV DNA but not HBV cccDNA in EPCs were detectable even 3 weeks after virus challenge, as shown by PCR analysis. Furthermore, intravenous transplantation of HBV-treated EPCs into myocardial infarction Sprague & Dawley rats model resulted in incorporation of both EPCs and HBV into injured endothelial tissues of capillaries in the ischemic border zone.


CONCLUSIONS
These results strongly support that EPCs serve as virus carrier mediating HBV trans-infection into the injured myocardial tissues. The findings might suggest a novel mechanism for HBV-associated myocarditis.
Rong
Qi-fei
QF
Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, China.
Huang
Jun
J
Su
En-ben
EB
Li
Jun
J
Li
Jian-yong
JY
Zhang
Li-li
LL
Chen
Lei-lei
LL
Wang
Xiao-bin
XB
Cao
Ke-jiang
KJ
D002465:Cell Movement; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D006321:Heart / Q000821:virology*; D006515:Hepatitis B virus / Q000502:physiology*; D006801:Humans; D018919:Neovascularization, Physiologic; D013234:Stem Cells / Q000502:physiology*