Human hepatoma HepG2 cells are susceptible to infection by domestic cat hepadnavirus

Domestic cat hepadnavirus (DCHBV; Hepadnaviridae , Orthohepadnavirus felisdomestici ) is a hepadnavirus identified in domestic cats that is associated with liver conditions that resemble hepatitis B virus (HBV) infections in humans. Despite its significance for feline health, research on DCHBV has been hindered due to the absence of suitable in vitro models, particularly the lack of feline hepatocyte cell lines. We found that cells of the human-derived hepatoma cell line, HepG2, were susceptible to DCHBV infection. DCHBV DNA and RNA were detected from the infected HepG2 cells at 48 h postinfection; DCHBV core protein and viral particles were detected within the infected cells. No significant enhancement of viral infection was observed by the addition of dimethyl sulfoxide or dexamethasone to the culture medium. However, higher levels of viral uptake were noted at 4 d postinfection when using a concentrated viral inoculum. Although HepG2 cells supported initial DCHBV infection, viral load declined over time during serial infection experiments. The DCHBV infection of HepG2 cells is limited and declines over successive passages, potentially due to insufficient cellular factors for sustained viral replication. Our findings establish a foundation for further investigations of DCHBV biology and highlight the necessity for identifying alternative cell lines to improve long-term infection models.