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Title: New models of hepatitis E virus replication in human and porcine hepatocyte cell lines

Author
item ROGEE, SOPHIE - Inland Northwest Research Alliance, Inra
item BOUQUET, JEROME - Inland Northwest Research Alliance, Inra
item BARNAUD, ELODIE - Inland Northwest Research Alliance, Inra
item PAVIO, NICOLE - Inland Northwest Research Alliance, Inra
item Talbot, Neil
item Caperna, Thomas

Submitted to: Journal of General Virology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/20/2012
Publication Date: 3/1/2013
Citation: Rogee, S., Bouquet, J., Barnaud, E., Pavio, N., Talbot, N.C., Caperna, T.J. 2013. New models of hepatitis E virus replication in human and porcine hepatocyte cell lines. Journal of General Virology. 94(3):549-558.

Interpretive Summary: Hepatitis E virus (HEV) causes acute, inflammation of the liver (hepatitis) and is spread by contaminated food and water. It is most prevalent in tropical and subtropical regions. Unlike other hepatitis viruses, HEV can infect several animals and it is likely that it can spread between these animal, such as pigs, and humans. The lack of efficient cell culture models, where cells grown and infected in vitro, i.e., in a petri dish, limits studies on molecular and cellular aspects of HEV infection and on the mechanisms of HEV’s spread between animals and humans. The present study reports on the development of two new in vitro models for studying HEV’s infection of cells and its reproduction in cells. The two in vitro models consist of (1), a human liver cancer-derived cell line, HepaRG, and (2), a porcine embryonic stem cell-derived cell line, PICM-19. These two cell lines have morphological and functional properties similar to primary liver cells. The study shows that these two in vitro culture systems support HEV reproduction and the release of viable virus particles. These new models represent a powerful tool for studying the viral reproduction cycle, how the viruses jumps from pigs to people, and what factors contribute to the severity of the infection, i.e., liver damage and death.

Technical Abstract: Hepatitis E virus (HEV) causes acute, enterically-transmitted hepatitis. It is associated with large epidemics in tropical and subtropical regions where it is endemic or with sporadic cases in non-endemic regions. Unlike other hepatitis viruses, HEV has several animal reservoirs. Phylogenetic studies on HEV human and animal sequences, and the identification of cases of direct transmission from animal to human strongly suggest that HEV is a zoonotic agent. The lack of efficient cell culture models limits studies on molecular and cellular aspects of HEV infection and species barrier crossing. The present study reports on the development of two new in vitro models of HEV replication using a human hepatoma-derived cell line, HepaRG, and a porcine embryonic stem cell-derived cell line, PICM-19. These two cell lines have morphological and functional properties similar to primary hepatocytes. These in vitro culture systems support HEV replication and release of encapsidated RNA. These new models represent a powerful tool for studying the viral replication cycle, species barrier crossing and virulence factors.