After receiving lamivudine for 3 years to treat chronic hepatitis B, 67-75% of patients develop B-domain L528M, C-domain M552I, or M552V mutations in the HBV polymerase that render hepatitis B virus (HBV) drug-resistant. The aim of this study was to evaluate the influence of these mutations on viral replication and resistance to antiviral agents. We investigated the replication fitness and susc...

The availability of nucleoside analogues has broadened treatment options for chronic hepatitis B virus (HBV ) infection. Registered treatment for chronic hepatitis B currently consists of (pegylated) interferon, lamivudine and adefovir, while entecavir is expected to be licensed in the short term. Treatment is generally recommended for patients with high serum HBV DNA and elevated ALAT, indicat...

CyaA is crucial for colonization by Bordetella pertussis, the etiologic agent of whooping cough. Here we report crystal structures of the adenylyl cyclase domain (ACD) of CyaA with the C-terminal domain of calmodulin. Four discrete regions of CyaA bind calcium-loaded calmodulin with a large buried contact surface. Of those, a tryptophan residue (W242) at an alpha-helix of CyaA makes extensive c...

The high levels of genetic diversity shown by hepatitis B virus (HBV) are commonly attributed to the low fidelity of its polymerase. However, the rate of spontaneous mutation of human HBV in vivo is currently unknown. Here, based on the evolutionary principle that the population frequency of lethal mutations equals the rate at which they are produced, we have estimated the mutation rate of HBV ...

We report the case of a male chronic hepatitis B virus (HBV) carrier with HLA-B27 spondyloarthrititis who developed fulminant hepatitis after discontinuation of methotrexate (MTX). Full recovery after therapy with lamivudine and adefovir allowed treatment with adalimumab which was well tolerated. Reactivation of hepatitis B after MTX withdrawal is a very rare complication, which can also occur ...

Treatment of chronic hepatitis B remains challenging due to medication-resistant viral mutations, unanswered questions for initiation and duration of treatment, and risk for chronic liver complications. More than 400 million people worldwide are chronically infected with hepatitis B virus (HBV).1 Of those, an estimated 1 million die annually of HBV-related liver diseases.1 In the past decade, H...