Host-pathogen interactions during in vitro hepatitis B virus infection

Hepatitis B virus (HBV) is a human pathogen that causes acute and chronic liver disease. While vaccination effectively prevents new infections, current antiviral therapies rarely eliminate HBV in chronically infected individuals, highlighting the need for improved treatment strategies. HBV depends on host cell functions for replication, and in this thesis, we investigated virus-host interactions during in vitro HBV infection. We used mass spectrometry (MS)-based proteomics to analyze how acute HBV infection influences the intracellular proteome and secretome of primary human hepatocytes (PHHs) eight days post infection. To distinguish changes associated with productive replication from those caused by non- infectious components of the viral inoculum or non-productive uptake of viral particles, we used HBV infection in the presence of the entry inhibitor bulevirtide (BLV) as a control. Once inoculum- and drug-related effects were accounted for, HBV replication induced only subtle changes in protein abundance, supporting the concept of HBV as a "stealth virus". Among the MS-identified proteins, reticulocalbin-2 (RCN2) was confirmed by orthogonal validation to be specifically downregulated during productive infection. Our results also showed that host-derived factors present in the inoculum can...