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A gene locus that controls expression of ACE2 in virus infection
M. Azim Ansari; Emanuele Marchi; Narayan Ramamurthy; Dominik Aschenbrenner; Carl-Philipp Hackstein; - STOP-HCV consortium; - ISARIC-4C Investigators; Shang-Kuan Lin; Rory Bowden; Eshita Sharma; Vincent Pedergnana; Suresh Venkateswaran; Subra Kugathasan; Angela Mo; Greg Gibson; John McLauchlan; Eleanor Barnes; John Kenneth Baillie; Sarah Teichmann; Alex Mentzer; John Todd; Julian Knight; Holm Uhlig; Paul Klenerman.
  • M. Azim Ansari; University of Oxford
  • Emanuele Marchi; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford OX1 3SY, UK
  • Narayan Ramamurthy; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford OX1 3SY, UK
  • Dominik Aschenbrenner; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DU, UK
  • Carl-Philipp Hackstein; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford OX1 3SY, UK
  • - STOP-HCV consortium; -
  • - ISARIC-4C Investigators; -
  • Shang-Kuan Lin; Wellcome Centre for Human Genetics, Roosevelt Dr, Headington, Oxford OX3 7BN
  • Rory Bowden; Wellcome Centre for Human Genetics, Roosevelt Dr, Headington, Oxford OX3 7BN
  • Eshita Sharma; Wellcome Centre for Human Genetics, Roosevelt Dr, Headington, Oxford OX3 7BN
  • Vincent Pedergnana; French National Centre for Scientific Research (CNRS), Laboratory MIVEGEC (CNRS, IRD, UM), Montpellier, France
  • Suresh Venkateswaran; Department of Pediatrics, Emory University School of Medicine and Children health care of Atlanta, Atlanta, USA
  • Subra Kugathasan; Department of Pediatrics, Emory University School of Medicine and Children health care of Atlanta, Atlanta, USA
  • Angela Mo; Center for Integrative Genomics, Georgia Institute of Technology, Atlanta, USA
  • Greg Gibson; Center for Integrative Genomics, Georgia Institute of Technology, Atlanta, USA
  • John McLauchlan; MRC-University of Glasgow Centre for Virus Research, Sir Michael Stoker Building, University of Glasgow, Glasgow, G61 1qh,
  • Eleanor Barnes; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford OX1 3SY, UK
  • John Kenneth Baillie; Genetics and Genomics, Roslin Institute, University of Edinburgh, Edinburgh EH25 9RG, UK.
  • Sarah Teichmann; Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton Cambridge, CB10 1SA UK
  • Alex Mentzer; Wellcome Centre for Human Genetics, Roosevelt Dr, Headington, Oxford OX3 7BN
  • John Todd; Wellcome Centre for Human Genetics, Roosevelt Dr, Headington, Oxford OX3 7BN
  • Julian Knight; Wellcome Centre for Human Genetics, Roosevelt Dr, Headington, Oxford OX3 7BN
  • Holm Uhlig; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford OX3 9DU, UK
  • Paul Klenerman; Peter Medawar Building for Pathogen Research, Nuffield Department of Medicine, University of Oxford, Oxford OX1 3SY, UK
Preprint En | PREPRINT-MEDRXIV | ID: ppmedrxiv-20080408
The SARS-CoV-2 pandemic has resulted in widespread morbidity and mortality globally. ACE2 is a receptor for SARS-CoV-2 and differences in expression may affect susceptibility to COVID-19. Using HCV-infected liver tissue from 195 individuals, we discovered that among genes negatively correlated with ACE2, interferon signalling pathways were highly enriched and observed down-regulation of ACE2 after interferon-alpha treatment. Negative correlation was also found in the gastrointestinal tract and in lung tissue from a murine model of SARS-CoV-1 infection suggesting conserved regulation of ACE2 across tissue and species. Performing a genome-wide eQTL analysis, we discovered that polymorphisms in the interferon lambda (IFNL) region are associated with ACE2 expression. Increased ACE2 expression in the liver was also associated with age and presence of cirrhosis. Polymorphisms in the IFNL region may impact not only antiviral responses but also ACE2 with potential consequences for clinical outcomes in distinct ethnic groups and with implications for therapeutic interventions.

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