To replicate efficiently, viruses must overcome innate defense mechanisms. Human APOBEC3G is a cytidine deaminase that represents one such barrier, conferring broad intracellular antiretroviral protection. The enzyme is packaged in virions and, during reverse transcription, deaminates deoxycytidine residues to deoxyuridine (dU) in the growing minus-strand of viral DNA. These dU-rich reverse transcripts are either degraded or yield proviruses that are largely nonfunctional due to G-to-A hypermutation (1). Most lentiviruses escape APOBEC3G inhibition via expression of a protein called Vif, which prevents the virion incorporation of the deaminase and triggers its proteasomal degradation (2). APOBEC3G is otherwise able to block a wide spectrum of distantly related retroviruses (3). To ask whether it can interfere with other retroelements, we examined its effect on hepatitis B virus (HBV).

HBV chronically infects more than 250 million individuals worldwide and is a leading cause of liver insufficiency and hepatocellular carcinoma. Retroviruses synthesize the proviral DNA mostly after they enter target cells. In contrast, HBV packages a partially double-stranded DNA genome produced by reverse transcription of pregenomic RNA within subviral core particles found in virus producer cells. Co-transfection of the Huh7 hepatoma cell line with an HBV-producing plasmid and APOBEC3G-expressing or control vectors led to comparable levels of viral transcription, translation, and extracellular production of HBsAg viral surface antigen (fig. S1, A to C). However, cells expressing the deaminase released at least 50 times less HBV DNA than control cells (fig. S1C). Correspondingly, there was a dose-dependent decrease in the levels of intracellular core-associated viral DNA in cells transfected with APOBEC3G, an effect that was completely abrogated by HIV-1 Vif (Fig. 1A; fig. S1D). APOBEC3G could be co-