In vivo antiviral efficacy of prenylation inhibitors against hepatitis delta virus
J. Clin. Invest. Bruno B. Bordier, et al. 112:407 doi:10.1172/JCI17704 [
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Figure 1Intrahepatic replication of HDV following hydrodynamic transfection. Mice transgenic for HBV were hydrodynamically transfected with vector DNA (pcDNA3) or a vector bearing HDV replication-inducing sequences [pCMV·HDVI(+)]. Seven days later, mice were sacrificed and liver samples were analyzed for HDV RNA and protein. (
a) Samples of total liver RNA from a mouse transfected with pcDNA3 (lane 1) or with pCMV·HDVI(+) (lane 2) were analyzed for HDV genomic RNA using Northern blots. Positions of molecular-weight markers are on the left; arrow indicates position of the replicated 1.7-kb RNA genome. (
b) Samples of total liver RNA from a mouse transfected with pcDNA3 (lane 1) or with pCMV·HDVI(+) (lane 2) were analyzed for delta antigen using Western blots. Positions of molecular-weight markers are on the left; arrow indicates position of delta antigen (δAg). (
c) Representative time course for HDV replication in hydrodynamically transfected mice. Mice transgenic for HBV were hydrodynamically transfected with pcDNA3 (lane 1) or pCMV·HDVI(+) (lanes 2–4) and were sacrificed at day 2 (lane 2), day 4 (lane 3), or day 7 (lanes 1 and 4) after transfection. Liver samples were analyzed for HDV RNA using Northern blots. To account for potential differences in transfection efficiency, a plasmid encoding hAAT was included in the transfection, and HDV replication was detected in mice who had similar serum levels of hAAT on day 2 after transfection. (
d and
e) Liver sections from the same mice as in
a were fixed in formalin and stained by immunohistochemistry for detection of HDV delta antigen. (
d) Mouse transfected with pcDNA3. (
e) Mouse transfected with pCMV·HDVI(+). Brown-red spots indicate characteristic nuclear staining pattern of delta antigen.