Dendritic cells take up viral antigens but do not support the early steps of hepatitis B virus infection.
Dendritic cells (DC) of hepatitis B virus (HBV) carriers have been reported to exhibit functional impairment. Possible explanations for this phenomenon are infection of HBV by DC or alteration of DC function by HBV. We therefore analyzed whether DC support the different steps of HBV infection and replication: uptake, deposition of the HBV genome in the nucleus, antigen expression, and progeny virus release. When HBV genomes were artificially introduced into monocyte-derived DC by adenoviral vectors, low-level expression of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) but no HBV replication was detected. When monocyte-derived DC were subjected to wild-type HBV or a recombinant HBV expressing Renilla luciferase under a non-liver-specific promoter, intracellular HBV DNA was detected in a low percentage of cells. However, neither nuclear cccDNA was formed nor luciferase activity was detected, indicating that either uncoating or nucleocytoplasmic transport were blocked. To verify our observation in the in vivo situation, myeloid and plasmacytoid DC were isolated from blood of high viremic HBV carriers, and analyzed by quantitative polymerase chain reaction (PCR) and electron microscopy. Although circulating DC had in vivo been exposed to more than 10(4) HBV virions per cell, HBV genomic DNA was hardly detected, and no nuclear cccDNA was detected at all. By using electron microscopy, subviral particles were found in endocytic vesicles, but virions were undetectable as were viral capsids in the cytoplasm. In conclusion, circulating DC may take up HBV antigens, but neither support nucleocytoplasmic transport nor replication of HBV.
Molecular Infectiology at the Center for Molecular Medicine, University of Cologne, Germany.
Andreas
A
Untergasser
Uta
U
Zedler
Anja
A
Langenkamp
Marianna
M
Hösel
Maria
M
Quasdorff
Knud
K
Esser
Hans-Peter
HP
Dienes
Barbara
B
Tappertzhofen
Waldemar
W
Kolanus
Ulrike
U
Protzer
D000256:Adenoviridae; D002353:Carrier State; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006509:Hepatitis B / Q000235:genetics / Q000276:immunology*; D006511:Hepatitis B Antigens / Q000302:isolation & purification*; D006515:Hepatitis B virus / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D014771:Virion / Q000235:genetics / Q000276:immunology; D014779:Virus Replication / Q000235:genetics / Q000276:immunology
D006511:Hepatitis B Antigens