Inhibitory effect of adefovir and lamivudine on the initiation of hepatitis B virus infection in primary tupaia hepatocytes.

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Kock J, Baumert TF, Delaney WE 4th, Blum HE, von Weizsacker F

Inhibitory effect of adefovir and lamivudine on the initiation of hepatitis B virus infection in primary tupaia hepatocytes.

Hepatology. 2003 Dec;38(6):1410-8.

PubMed ID

14647052 [ View in PubMed

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Abstract

Adefovir dipivoxil and lamivudine are two safe and efficacious drugs licensed for the treatment of chronic hepatitis B virus (HBV) infection. Both drugs inhibit the viral polymerase, resulting in a profound suppression of virus production. Blocking the viral polymerase may also affect the initiation of HBV infection, because HBV virions harbor a partially double-stranded genome and productive infection requires completion of viral plus-strand DNA synthesis with subsequent formation of covalently closed circular DNA (cccDNA). To address this issue, we used primary hepatocytes from the tree shrew Tupaia belangeri that were recently shown to be susceptible to HBV infection. Treatment of cells with either drug partially inhibited initial HBV cccDNA formation. Adefovir was more effective than lamivudine, resulting in a 3-fold reduction of RNA synthesis and viral surface antigen production. However, prevention of initial cccDNA formation was incomplete even after combined treatment, whereas de novo synthesis of viral replicative intermediates was completely suppressed. A possible explanation for this observation is the genomic plus-strand gap of less than 200 bases in some virions, limiting the window for antiviral action. In conclusion, nucleos(t)ide analogues can target initial plus-strand DNA repair and reduce but not completely block HBV infection.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Adefovir	DNA polymerase/reverse transcriptase	Protein	HBV-D	Yes	Inhibitor	Details
Adefovir dipivoxil	DNA polymerase/reverse transcriptase	Protein	HBV-D	Yes	Other	Details