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A Highly Divergent Picornavirus Infecting the Gut Epithelia of 1,6 1,2 7 7 1,2* Sadeghi , Xutao Deng , Erica K

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A Highly Divergent Picornavirus Infecting the Gut Epithelia of 1,6 1,2 7 7 1,2* Sadeghi , Xutao Deng , Erica K bioRxiv preprint first posted online Nov. 5, 2018; doi: http://dx.doi.org/10.1101/463083. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. bioRxiv preprint first posted online Nov. 5, 2018; doi: http://dx.doi.org/10.1101/463083. The copyright holder for this preprint (which wasA not highly peer-reviewed) divergent is the author/funder, picornavirus who has granted bioRxiv a infectinglicense to display the the preprint gut in perpetuity. epithelia of All rights reserved. No reuse allowed without permission. zebrafish (Danio rerio) in research institutions world-wide Eda Altan1,2, Steven V. Kubiski3, Ákos Boros4,5, Gábor Reuter5, Mohammadreza A highly divergent picornavirus infecting the gut epithelia of 1,6 1,2 7 7 1,2* Sadeghi , Xutao Deng , Erica K. Creighton , Marcus J. Crim , Eric Delwart zebrafish (Danio rerio) in research institutions world-wide Eda Altan1,2, Steven V. Kubiski3, Ákos Boros4,5, Gábor Reuter5, Mohammadreza 1 Vitalant Research Institute, San Francisco, CA 94118, USA 2 1,6 1,2 7 7 1,2* SadeghiDept. of, LaboratoryXutao Deng Medicine,, Erica K. University Creighton of ,California,Marcus J. SanCrim Francisco,, Eric Delwart CA 94118, USA 3 Institute for Conservation Research, San Diego Zoo Global, San Diego, CA, 92112, USA 4 1 VitalantRegional Research Laboratory Institute, of Virology, San Francisco, National CAReference 94118, LaboratoryUSA of Gastroenteric Viruses, ÁNTSZ Regional Institute of State Public Health Service, Pécs, Hungary 2 Dept. of Laboratory Medicine, University of California, San Francisco, CA 94118, USA 5 Department of Medical Microbiology and Immunology, Medical School, University of 3 Institute for Conservation Research, San Diego Zoo Global, San Diego, CA, 92112, Pécs, Pécs, Hungary USA 4 6 Department of Virology, University of Helsinki, Helsinki, Finland. Regional7 Laboratory of Virology, National Reference Laboratory of Gastroenteric Viruses, IDEXX ÁNTSZ BioAnalytics, Regional Columbia, Institute ofMO State 65201-8250, Public Health USA Service, Pécs, Hungary 5 Department of Medical Microbiology and Immunology, Medical School, University of Pécs, Pécs, Hungary 6 Department*corresponding of Virology, author: [email protected] of Helsinki, Helsinki, Finland. 7 IDEXX BioAnalytics, Columbia, MO 65201-8250, USA Phone: (415) 923-5763 *corresponding author: Fax: [email protected] (415) 567-5899 Phone: (415) 923-5763 Fax: (415) 567-5899 1 1 bioRxiv preprint first posted online Nov. 5, 2018; doi: http://dx.doi.org/10.1101/463083. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. bioRxiv preprint first posted online Nov. 5, 2018; doi: http://dx.doi.org/10.1101/463083. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. A highly divergent picornavirus infecting the gut epithelia of Abstract zebrafish (Danio rerio) in research institutions world-wide Zebrafish have been extensively used as a model system for research in vertebrate Eda Altan1,2, Steven V. Kubiski3, Ákos Boros4,5, Gábor Reuter5, Mohammadreza development and pathogen-host interactions. We describe the complete genome of a 1,6 1,2 7 7 1,2* novelSadeghi picornavirus, Xutao identified Deng , Ericaduring K. a Creightonviral metagenomics, Marcus J.analysis Crim , ofEric zebrafish Delwart gut tissue. The closest relatives of this virus showed identity of <19.8% in their P1 capsids and1 Vitalant<35.4% Research in their RdRp Institute, qualifying San Francisco,zebrafish picornavirus CA 94118, 1 USA (ZfPV1) as member of a 2 novelDept. genus of Laboratory with a proposed Medicine, name University of Cyprivirus. of California,RT-PCR testing San Francisco, of zebrafish CA from 94118, 41 USA 3 Institute for Conservation Research, San Diego Zoo Global, San Diego, CA, 92112, institutionsUSA from North America, Europe, and Asia showed ZfPV1 to be highly prevalent 4 world-wide.Regional InLaboratory situ hybridization of Virology, of whole National zebrafish Reference showed Laboratory viral RNA was of Gastroenteric restricted to Viruses, ÁNTSZ Regional Institute of State Public Health Service, Pécs, Hungary a subset of enterocytes and cells in the subjacent lamina propria of the intestine and the 5 Department of Medical Microbiology and Immunology, Medical School, University of intestinalPécs, Pécs, mucosa Hungary. This naturally occurring and apparently asymptomatic infection (in 6 Department of Virology, University of Helsinki, Helsinki, Finland. wild type zebrafish lineage AB) provides a natural infection system to study 7 IDEXX BioAnalytics, Columbia, MO 65201-8250, USA picornavirus-host interactions in an advanced vertebrate model organism. Whether ZfPV1 infection affects any immunological, developmental or other biological processes *corresponding author: [email protected] in wild type or mutant zebrafish lineages remains to be determined. Phone: (415) 923-5763 Fax: (415) 567-5899 2 1 bioRxiv preprint first posted online Nov. 5, 2018; doi: http://dx.doi.org/10.1101/463083. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. bioRxiv preprint first posted online Nov. 5, 2018; doi: http://dx.doi.org/10.1101/463083. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. A highly divergent picornavirus infecting the gut epithelia of Introduction zebrafish (Danio rerio) in research institutions world-wide Picornaviruses are small non-enveloped viruses with positive-sense, genomic Eda Altan1,2, Steven V. Kubiski3, Ákos Boros4,5, Gábor Reuter5, Mohammadreza single-stranded RNA ranging in size from 6.7 kb to 10.1 kb (www.picornaviridae.com). 1,6 1,2 7 7 1,2* TheSadeghi Picornaviridae, Xutao familyDeng currently, Erica K.includes Creighton 35 genera, Marcus andJ. >75 Crim species, Eric plusDelwartseveral candidate genera [1,2] and have been detected in diverse vertebrate hosts including fish1 Vitalant (Bluegill Research picornavirus Institute, [3], SanEel picornavirusFrancisco, CA [4], 94118, Carp USApicornavirus [5], Fathead 2 minnowDept. picornavirusof Laboratory [6] Medicine,and unassigned University fish picornaviruses of California, [ 7San]). Francisco, CA 94118, USA 3 Institute for Conservation Research, San Diego Zoo Global, San Diego, CA, 92112, USA Except for the Dicipivirus genus [8,9] with two IRES and open reading frames 4 (ORFs),Regional typical Laboratory picornavirus of Virology, genomes National contain Reference a single Laboratory ORF encoding of Gastroenteric a large Viruses, ÁNTSZ Regional Institute of State Public Health Service, Pécs, Hungary polyprotein flanked by 5’ and 3’ untranslated regions (UTRs)[8]. The viral genome 5 Department of Medical Microbiology and Immunology, Medical School, University of organizationPécs, Pécs, is Hungaryas follows: the N terminal P1 region encodes the structural proteins such 6 Department of Virology, University of Helsinki, Helsinki, Finland. as viral capsid proteins and the P2 and P3 regions encode nonstructural proteins 7 IDEXX BioAnalytics, Columbia, MO 65201-8250, USA involved in polyprotein processing and genome replication. The laboratory zebrafish, Danio rerio, is a member of the minnow family *corresponding author: [email protected] (Cyprinidae), that initially gained importance as a developmental genetics model and has since expanded Phone: into a wide(415) range 923-5763 of biomedical research areas, including behavior, cancer, infection and immunology, pathogenesis, toxicology, and drug discovery. Fax: (415) 567-5899 Importantly, the zebrafish has recently emerged as a valuable animal model for pathogen-host interactions for several reasons, including genetic tractability with a completely sequenced and well-annotated genome [10], a vertebrate immune system with developmental separation between innate and adaptive immune responses [11,12], the capacity to facilitate temperature-shift experiments [13], and exceptional utility for imaging, that allows infected cells and immune cells to be visualized at high resolution 3 1 bioRxiv preprint first posted online Nov. 5, 2018; doi: http://dx.doi.org/10.1101/463083. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. bioRxiv preprint first posted online Nov. 5, 2018; doi: http://dx.doi.org/10.1101/463083. The copyright holder for this preprint (which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. A highly divergent picornavirus infecting the gut epithelia of throughout the entire living organism [14,15]. These characteristics of the zebrafish as zebrafish (Danio rerio)
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