Project Description

TP22: Impact of the enteric stage of hepatitis A virus and hepatitis E virus on the outcome of liver infection

Enterically transmitted Hepatitis A virus (HAV) and hepatitis E virus (HEV) are the leading causes of acute viral hepatitis in developing countries. During the natural spreading of HAV and HEV along the gut-liver axis, viruses must enter intestinal epithelial cells by their apical side and de novo viruses have to be released from their basolateral side en route to the liver. Once in the liver, these viruses will infect hepatocytes from their basolateral side and de novo virus particles will be released back into the gastro-intestinal tract by polarized apical secretion into the bile canaliculi. In this proposal, the long term aims are to address how the enteric phase of the HAV and HEV life cycle impacts virus replication and spread in the liver and ultimately whether this contributes to the acute nature of HAV and HEV infection
Dao Thi VL, Wu X, Belote RL, Andreo U, Takacs CN, Fernandez JP, Vale-Silva LA, Prallet S, Decker CC, Fu RM, Qu B, Uryu K, Molina H, Saeed M, Steinmann E, Urban S, Singaraja RR, Schneider WM, Simon SM, Rice CM. Stem cell-derived polarized hepatocytes. Nat Commun. 2020 Apr 3;11(1):1677. doi: 10.1038/s41467-020-15337-2. (TP22, TP15)
A. Stanifer ML, Kee C, Cortese M, Zumaran CM, Triana S, Mukenhirn M, Kraeusslich HG, Alexandrov T, Bartenschlager R, Boulant S. 2020. Critical Role of Type III Interferon in Controlling SARS-CoV-2 Infection in Human Intestinal Epithelial Cells. Cell Rep. 2020 Jul 7;32(1):107863. doi: 10.1016/j.celrep.2020.107863 (TP09, TP22)
B. Muenchau S, Deutsch R, de Castro IJ, Hielscher T, Heber N, Niesler B, Lusic M, Stanifer ML, Boulant S. 2019. Hypoxic environment promotes barrier formation in human intestinal epithelial cells through regulation of miRNA-320a expression. Mol. Cell. Biol 39(14). pii: e00553-18
C. Gouttenoire J, Pollán A, Abrami L, Oechslin N, Mauron J, Matter M1, Oppliger J, Szkolnicka D, Dao Thi VL, van der Goot FG, Moradpour D. 2018. Palmitoylation mediates membrane association of hepatitis E virus ORF3 protein and is required for infectious particle secretion PLoS Pathog. 14(12):e1007471.
D. Dao Thi VL, Wu X, Rice CM. 2019. Stem Cell-Derived Culture Models of Hepatitis E Virus Infection. Cold Spring Harb Perspect Med. pii: a03179
E. Pervolaraki K, Rastgou Talemi S, Albrecht D, Bormann F, Bamford C, Mendoza JL, Garcia KC, McLauchlan J, Höfer T, Stanifer ML, Boulant S. 2018. Differential induction of interferon stimulated genes between type I and type III interferons is independent of interferon receptor abundance. PLoS Pathog. 14(11):e1007420.
F. Wu X*, Dao Thi VL*, Liu P, Takacs CN, Xiang K, Andrus L, Gouttenoire J, Moradpour D, Rice CM 2018. Pan-Genotype Hepatitis E Virus Replication in Stem Cell-Derived Hepatocellular Systems. Gas-troenterology. 154(3):663-674.e7
G. Wu X, Dao Thi VL, Huang Y, Billerbeck E, Saha D, Hoffmann HH, Wang Y, Vale Silva LA, Sarbanes S, Sun T, Andrus L, Quirk C, MacDonald MR, Schneider WM, An X, Rosenberg BR, Rice CM. 2018. Intrinsic Immunity Shapes Viral Resistance of Stem Cells. Cell. 172(3):423-438.e25
H. Pervolaraki K, Stanifer ML, Münchau S, Renn LA., Albrecht D, Kurzhals S, Senís E, Grimm D, Schrö-der-Braunstein J, Rabin RL, Boulant S. 2017. Type I and Type III Interferons Display Different De-pendency on Mitogen-Activated Protein Kinases to Mount an Antiviral State in the Human Gut. Front Immunol. 8: 459
I. Stanifer ML, Rippert A, Kazakov A, Willemsen J, Bucher D, Bender S, Bartenschlager R, Binder M, Boulant S. 2016. Reovirus intermediate subviral particles constitute a strategy to infect intestinal epi-thelial cells by exploiting TGF-β dependent pro-survival signaling. Cell. Microbiol. 18(12): 1831–1845.
J. Dao Thi VL, Debing Y, Wu X, Rice CM, Neyts J, Moradpour D*, Gouttenoire J*. 2016. Sofosbuvir inhibits Hepatitis E virus replication in vitro and results in an additive effect when combined with rib-avirin. Gastroenterology. 150(1):82-85.