Publications & Reports

Hepatocytes traffic and export hepatitis B virus basolaterally by polarity-dependent mechanisms.

Bhat P, Snooks MJ, Anderson DA
Ian Potter Hepatitis Research Laboratory, Macfarlane Burnet Institute for Medical Research and Public Health, 85 Commercial Rd, Melbourne, 3004. Australia.

Abstract

Full text is available at this URL http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3209395/pdf/zjv12474.pdf

Viruses commonly utilize the cellular trafficking machinery of polarized cells to effect viral export. Hepatocytes are polarized in vivo, but most in vitro hepatocyte models are either non-polarized, or have morphology unsuitable for the study of viral export. Here, we investigate the mechanisms of trafficking and export for the hepadnaviruses, hepatitis B virus (HBV) and duck hepatitis B virus (DHBV), in polarized hepatocyte-derived cell lines and primary duck hepatocytes. DHBV export, but not replication, was dependent on the development of hepatocyte polarity, with export significantly abrogated over time as primary hepatocytes lost polarity. Using Transwell cultures of polarized N6 cells and Adenovirus-based transduction, we observed that export of both HBV and DHBV was vectorially regulated and predominantly basolateral. Monitoring of polarized N6 cells and non-polarized C11 cells during persistent, long-term DHBV infection demonstrated that newly synthesized sphingolipid and virus displayed significant co-localization and FRET, implying co-transportation from the Golgi to the plasma membrane. Notably, 15% of virus was released apically from polarized cells, corresponding to secretion into the bile duct in vivo, also in association with sphingolipids. We conclude that DHBV, and probably HBV, is reliant upon hepatocyte polarity to be efficiently exported, and this export is in association with sphingolipid structures, possibly lipid rafts. This study provides novel insights regarding the mechanisms of hepadnavirus trafficking in hepatocytes, with potential relevance to pathogenesis and immune tolerance.

Publication

  • Journal: Journal of Virology
  • Published: 21/09/2011
  • Volume: 85
  • Issue: 23
  • Pagination: 12474-12481

Author