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A New Variant of Hepatitis A Virus Causing Transient Liver Enzyme Elevations in Mauritius-origin Laboratory-housed Cynomolgus macaques

View ORCID ProfileLars Mecklenburg, Rebecca Ducore, Molly Boyle, Andrew Newell, Laura Boone, Joerg Luft, Annette Romeike, Ann-Kathrin Haverkamp, Keith Mansfield, JJ Baczenas, Nick Minor, Shelby L. O’Connor, View ORCID ProfileDavid H. O’Connor
doi: https://doi.org/10.1101/2022.11.18.515766
Lars Mecklenburg
1Labcorp Early Development Services GmbH, 48163 Muenster, Germany
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  • For correspondence: lars.mecklenburg@labcorp.com
Rebecca Ducore
2Labcorp Early Development Laboratories Inc., Chantilly, VA 20151, USA
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Molly Boyle
3Labcorp Early Development Laboratories Inc., Somerset, NJ 08873, USA
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Andrew Newell
4Labcorp Early Development Laboratories Ltd., Harrogate, HG3 1PY, United Kingdom
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Laura Boone
5Labcorp Early Development Laboratories Inc., Greenfield, IN 46140, USA
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Joerg Luft
1Labcorp Early Development Services GmbH, 48163 Muenster, Germany
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Annette Romeike
1Labcorp Early Development Services GmbH, 48163 Muenster, Germany
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Ann-Kathrin Haverkamp
1Labcorp Early Development Services GmbH, 48163 Muenster, Germany
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Keith Mansfield
6Novartis Institutes for BioMedical Research; Cambridge, MA 02139, USA
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JJ Baczenas
7University of Wisconsin-Madison, Madison, WI 53706, USA
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Nick Minor
7University of Wisconsin-Madison, Madison, WI 53706, USA
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Shelby L. O’Connor
7University of Wisconsin-Madison, Madison, WI 53706, USA
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David H. O’Connor
7University of Wisconsin-Madison, Madison, WI 53706, USA
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  • ORCID record for David H. O’Connor
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ABSTRACT

Hepatitis A virus (HAV) infects humans and non-human primates causing an acute self-limited illness. Three HAV genotypes have been described for humans and three genotypes have been described for non-human primates. We observed transiently elevated liver enzymes in Mauritius-origin laboratory-housed macaques in Germany and were not able to demonstrate HAV by serology and PCR. Using deep sequencing, we have identified a new HAV genotype with 86% nucleotide sequence homology to HAV genotype IV capsid proteins and approximately 80% nucleotide homology to other HAV genotypes. In situ hybridization indicates persistence in the biliary epithelium up to 3 months after liver enzymes were elevated. Vaccination using a commercial vaccine against human HAV prevented reoccurrence of liver enzyme elevations. Since available assays for HAV did not detect this new variant, knowledge of its existence may ameliorate potential significant epidemiological and research implications in laboratories globally.

Article Summary Line A new genotype of hepatitis A virus, that was not identifiable by available diagnostic assays, caused liver enzyme elevations in laboratory-housed Mauritius-origin Cynomolgus macaques.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Conflict of interests: The authors declare no conflicts of interest.

  • Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

  • Meeting(s) where the information has previously been presented: The information provided in this manuscript has previously not been presented.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted November 18, 2022.
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A New Variant of Hepatitis A Virus Causing Transient Liver Enzyme Elevations in Mauritius-origin Laboratory-housed Cynomolgus macaques
Lars Mecklenburg, Rebecca Ducore, Molly Boyle, Andrew Newell, Laura Boone, Joerg Luft, Annette Romeike, Ann-Kathrin Haverkamp, Keith Mansfield, JJ Baczenas, Nick Minor, Shelby L. O’Connor, David H. O’Connor
bioRxiv 2022.11.18.515766; doi: https://doi.org/10.1101/2022.11.18.515766
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A New Variant of Hepatitis A Virus Causing Transient Liver Enzyme Elevations in Mauritius-origin Laboratory-housed Cynomolgus macaques
Lars Mecklenburg, Rebecca Ducore, Molly Boyle, Andrew Newell, Laura Boone, Joerg Luft, Annette Romeike, Ann-Kathrin Haverkamp, Keith Mansfield, JJ Baczenas, Nick Minor, Shelby L. O’Connor, David H. O’Connor
bioRxiv 2022.11.18.515766; doi: https://doi.org/10.1101/2022.11.18.515766

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