Hepatocytes that express variants of cyclophilin A are resistant to HCV infection and replication

Gastroenterology
Thomas von HahnSandra Ciesek

Abstract

Hepatitis C virus (HCV) uses several host factors to infect and replicate in human hepatocytes. Cyclophilin A (CypA) is required for viral replication, and CypA inhibitors are in development. We investigated the effects of nonsynonymous single nucleotide polymorphisms (SNPs) in the region of peptidyl-prolyl isomerase A (PPIA) that encodes CypA on HCV infection and replication of human hepatocytes. We used a combination of virologic, biochemical, and genetic approaches to investigate the effects of PPIA variants on HCV replication in cultured Huh-7.5 cells. We reduced levels of CypA in these cells using small hairpin RNAs (shRNAs). Using shRNAs, we showed that CypA was required for replication of HCV in Huh-7.5 cells and identified 3 SNPs in PPIA that protected cells from HCV entry or replication. Levels of HCV RNA were reduced 3-4 log in cells homozygous for the variant alleles; release of new particles was also reduced, but viral entry was not affected. The effects of the variant alleles were recessive and stronger for preventing replication of full-length HCV genomes than subgenomes. CypA inhibitors prevented replication of residual HCV in hepatocytes. The variants appeared to destabilize the CypA protein; the single amino ac...Continue Reading

References

Mar 21, 2003·Biophysical Chemistry·Jörg Fanghänel, Gunter Fischer
May 16, 2006·Journal of Virology·George KoutsoudakisRalf Bartenschlager
Dec 18, 2008·The Journal of General Virology·Jeroen WitteveldtArvind H Patel
Jan 17, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Judith M GottweinJens Bukh
Apr 22, 2009·The Journal of Biological Chemistry·Udayan ChatterjiPhilippe Gallay
Sep 5, 2009·The Journal of Clinical Investigation·Alexandre AlcaïsJean-Laurent Casanova
Sep 15, 2009·Nature Genetics·Vijayaprakash SuppiahJacob George
Sep 18, 2009·Nature·David L ThomasMary Carrington
Oct 13, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sandra CiesekThomas Pietschmann
Feb 9, 2010·Expert Review of Gastroenterology & Hepatology·Thomas von HahnThomas Pietschmann
Feb 16, 2010·Gastroenterology·Sandra CiesekThomas Pietschmann
May 14, 2010·Journal of Virology·Indu KohaarLudmila Prokunina-Olsson
Nov 26, 2010·Clinical Microbiology and Infection : the Official Publication of the European Society of Clinical Microbiology and Infectious Diseases·D Lavanchy
Feb 5, 2011·Nature Reviews. Gastroenterology & Hepatology·Sandra Ciesek, Michael P Manns
Mar 16, 2011·Proceedings of the National Academy of Sciences of the United States of America·Megan M DringClair M Gardiner
Jun 10, 2011·The Journal of Antimicrobial Chemotherapy·Vincent SorianoPablo Barreiro

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Citations

Jul 16, 2013·Viruses·Stephen D FraustoHengli Tang
Oct 23, 2012·Current Opinion in Virology·Ana Shulla, Glenn Randall
Sep 1, 2015·Current Opinion in Virology·Albrecht von BrunnJavier Carbajo-Lozoya
Aug 19, 2015·Current Opinion in Virology·Thomas von Hahn, Sandra Ciesek
Mar 13, 2014·Journal of Viral Hepatitis·P B SugdenUNKNOWN HITS Investigators
Feb 24, 2015·The Lancet Infectious Diseases·Michael M MinaAndrew R Lloyd
Mar 21, 2017·Journal of Proteome Research·Alessandra VidottoMauricio L Nogueira
Jan 20, 2016·World Journal of Hepatology·Ronik Khachatoorian, Samuel W French
Jun 23, 2019·Scientific Reports·Luis Miguel RealUNKNOWN GEHEP 012 study group
Jan 1, 2013·Current Hepatitis Reports·Gisa Gerold, Thomas Pietschmann

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