Liver-related mortality is increased in the setting of HIV-hepatitis B virus (HBV)
coinfection. However, interactions between HIV and HBV to explain this observation have not been described. We hypothesized that
HIV infection of hepatocytes directly affects the life cycle of HBV. We infected human hepatic cell lines expressing HBV (Hep3B and AD38 cells) or not expressing HBV (Huh7, HepG2, and AD43 cells) with laboratory strains of HIV (NL4-3 and AD8), as well as a
vesicular stomatitis virus (VSV)-pseudotyped HIV expressing
enhanced green fluorescent protein (EGFP). Following
HIV infection with NL4-3 or AD8 in hepatic cell lines, we observed a significant increase in
HIV reverse transcriptase activity which was infectious. Despite no detection of surface CD4, CCR5, and CXCR4 by flow cytometry, AD8
infection of AD38 cells was inhibited by
maraviroc and NL4-3 was inhibited by
AMD3100, demonstrating that HIV enters AD38 hepatic cell lines via CCR5 or CXCR4. High-level
infection of AD38 cells (50%) was achieved using VSV-pseudotyped HIV.
Coinfection of the AD38 cell line with HIV did not alter the HBV
DNA amount or species as determined by Southern blotting or
nucleic acid signal amplification. However,
coinfection with HIV was associated with a significant increase in intracellular
HBsAg when measured by Western blotting, quantitative
HBsAg, and fluorescence microscopy. We conclude that
HIV infection of HBV-infected hepatic cell lines significantly increased intracellular
HBsAg but not HBV
DNA synthesis and that increased intrahepatic
HBsAg secondary to direct
infection by HIV may contribute to accelerated
liver disease in HIV-HBV-coinfected individuals.