At Least Seven Distinct Rotavirus Genotype Constellations in Bats with Evidence Of
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bioRxiv preprint doi: https://doi.org/10.1101/2020.08.13.250464; this version posted August 15, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 1 At least seven distinct rotavirus genotype constellations in bats with evidence of 2 reassortment and zoonotic transmissions 3 4 Ceren Simseka; Victor Max Cormanb,o; Hermann Ulrich Everlingc; Alexander N. 5 Lukashevd; Andrea Rascheb,o; Gael Darren Magangae,f; Tabea Bingeri; Daan Jansena; 6 Leen Bellera; Ward Debouttea; Florian Gloza-Rauschg; Antje Seebens-Hoyerg; Stoian 7 Yordanovh; Augustina Sylverkeni,j; Samuel Oppongj; Yaw Adu Sarkodiej; Peter Vallok; 8 Eric M. Leroyl; Mathieu Bourgarelm,n,; Kwe Claude Yindaa*; Marc Van Ransta; Christian 9 Drostenb,o; Jan Felix Drexlerb,o; Jelle Matthijnssensa 10 11 a KU Leuven - University of Leuven, Department of Microbiology, Immunology and 12 Transplantation, Rega Institute for Medical Research, Leuven, Belgium 13 b Charité-Universitätsmedizin Berlin, corporate member 14 of Freie Universität Berlin, Humbolt-Universität zu Berlin and Berlin Institute of Health, 15 Institute of Virology, 10117 Berlin, Germany 16 c Institute of Virology, University of Bonn Medical Centre, Bonn, Germany 17 d Sechenov University, Moscow, Russia 18 e Centre International de Recherches Médicales de Franceville, Franceville, Gabon 19 f Université des Sciences et Technique de Masuku, Institut National d’Agronomie et de 20 Biotechnologies, Franceville, Gabon 21 g Noctalis, Centre for Bat Protection and Information, Bad Segeberg, Germany 22 h Forestry Board Directorate of Strandja Natural Park, Malko Tarnovo, Bulgaria 23 i Kumasi Centre for Collaborative Research in Tropical Medicine (KCCR), Kumasi, 24 Ghana 1 bioRxiv preprint doi: https://doi.org/10.1101/2020.08.13.250464; this version posted August 15, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 25 j Kwame Nkrumah University of Science and Technology, Kumasi, Ghana 26 k Institute of Vertebrate Biology, Academy of Sciences of the Czech Republic, v.v.i., 27 Brno 28 l Institut de Recherche pour le Développement, UMR 224 (MIVEGEC), 29 IRD/CNRS/Montpellier University, Montpellier, France 30 m CIRAD, UMR ASTRE, Harare, Zimbabwe 31 n ASTRE, Montpellier University, CIRAD, INRA, Montpellier, France 32 o German Centre for Infection Research (DZIF), associated partner Charité 33 Universitätsmedizin Berlin, 10117 Berlin, Germany 34 35 Running title: Genetic diversity of bat rotaviruses 36 37 #Address correspondence to Jelle Matthijnssens, [email protected]; Jan 38 Felix Drexler: [email protected] 39 40 Ceren Simsek, Victor Max Corman and Hermann Ulrich Everling contributed equally to 41 this work. Author order was determined on mutual agreement. 42 43 *Present address: Laboratory of Virology, Rocky Mountain Laboratories, Division of 44 Intramural Research, National Institute of Allergy and Infectious Diseases, National 45 Institutes of Health, Hamilton, Montana, USA 46 47 Abstract: 250 words 48 Text: 5114 words 2 bioRxiv preprint doi: https://doi.org/10.1101/2020.08.13.250464; this version posted August 15, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 49 ABSTRACT 50 Bats host many viruses pathogenic to humans, and increasing evidence suggests that 51 Rotavirus A (RVA) also belongs to this list. Rotaviruses cause diarrheal disease in many 52 mammals and birds, and their segmented genomes allow them to reassort and increase 53 their genetic diversity. Eighteen out of 2,142 bat faecal samples (0.8%) collected from 54 Europe, South America and Africa were PCR-positive for RVA and 11 of those were fully 55 characterized using viral metagenomics. Upon contrasting their genomes with publicly 56 available data, at least 7 distinct bat RVA genotype constellations were identified, 57 including evidence of reassortments among them. Some of these constellations are 58 spread across the world, whereas others appear to be geographically restricted. Our 59 analyses also provide evidence for multiple zoonotic transfer events involving bat RVAs. 60 A Bulgarian bat RVAs possessed a genotype constellation previously identified in Chinese 61 bats, and identical to a rare Argentinean horse RVA. A Costa Rican bat RVA possessed 62 3 previously undescribed gene segments and clustered closely with a human strain. 63 Although SA11 is one of the most widely used reference strains for RVA research and 64 forms the backbone of a reverse genetics system, its origin remained enigmatic. 65 Remarkably, the majority of the gene segments of SA11 were closely related to Gabonese 66 bat RVAs, suggesting a potential bat origin. Overall, our findings suggest an 67 underexplored genetic diversity of RVAs in bats which is likely the tip of the iceberg. 68 Increasing contact between humans and bat wildlife will further increase the zoonosis risk, 69 which warrants closer attention to these viruses. 70 71 Importance 3 bioRxiv preprint doi: https://doi.org/10.1101/2020.08.13.250464; this version posted August 15, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 72 The increased research on bat coronaviruses after SARS-CoV and MERS-CoV, allowed 73 the very rapid identification of SARS-CoV-2. This is an excellent example of the 74 importance of knowing viruses harboured by wildlife in general and bats in particular, for 75 global preparedness against emerging viral pathogens. The current effort to characterise 76 bat rotavirus strains from 3 continents provided evidence that several atypical rotaviruses 77 in humans and animals might have a bat origin, implying that zoonoses of bat rotaviruses 78 occur more frequently than currently realized. 79 80 Keywords: Viral metagenomics, bat rotavirus, rotavirus genetic diversity, SA11, zoonosis 81 82 Author Contributions 83 C.D, J.F.D, J.M and M.V.R designed the research; V.M.C., H.U.E., A.N.L., A.R., G.D.M., 84 T.B., F.G.R., A.SH., S.Y., A.S, S.O., Y.A.S., P.V., M.B. and E.M.L. were involved in 85 sample collection; V.M.C., H.U.E., A.N.L. and C.S. performed the research; C.S., D.J., 86 L.B., W.D., H.U.E., V.M.C. and K.C.Y. contributed in data analysis; J.F.D., C.D., C.S. and 87 J.M. drafted the paper; final version was approved by all co-authors. 88 4 bioRxiv preprint doi: https://doi.org/10.1101/2020.08.13.250464; this version posted August 15, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 89 INTRODUCTION 90 Rotaviruses are the leading cause of diarrheal disease in the young of mammals and 91 birds. In humans, rotaviruses are responsible for 122,000-216,000 deaths in under 5-year 92 old infants on a yearly basis, mainly in developing countries (1). The Rotavirus genus 93 belongs to the family Reoviridae and contains 9 species designated as A-I (RVA-RVI). 94 The rotavirus genome consists of 11 dsRNA segments encoding 6 structural viral proteins 95 (VP1-6) and 6 non-structural proteins (NSP1-6) (2). 96 The RVA outer capsid antigens, VP4 and VP7 are used for a dual classification system 97 defining P-genotype (VP4 is Protease sensitive) and G-genotype (VP7 is Glycosylated), 98 respectively (2). However, as gene reassortment is a common phenomenon for viruses 99 with a segmented genome after co-infection, a more comprehensive classification 100 approach became necessary to better account for the genome evolution and genetic 101 diversity of RVAs. In 2008, a nucleotide sequence-based, complete genome classification 102 system was developed for RVA, define genotypes for each of the 11 gene segment. These 103 genotypes allowed extending the dual classification to full ‘genotype constellations’ 104 classification (3, 4). The gene assignments are reported as Gx-P[x]-Ix-Rx-Cx-Mx-Ax-Nx- 105 Tx-Ex-Hx, where ‘x’ denotes the particular genotype. The Rotavirus Classification Working 106 Group (RCWG) was formed in order to assign new genotypes to rotavirus genes which 107 could not be assigned to an established genotype (5). A web-based RotaC tool that uses 108 the pre-set nucleotide cut-off values was also developed for automated genotype 109 assignment (6). 110 Accumulating whole genome sequencing data demonstrate that there are typical 111 genotype constellations present in most animal species. Two of them, Wa-like and DS-1- 112 like, are responsible for most of the human disease and designated as I1-R1-C1-M1-A1- 5 bioRxiv preprint doi: https://doi.org/10.1101/2020.08.13.250464; this version posted August 15, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC-ND 4.0 International license. 113 N1-T1-E1-H1 and I2-R2-C2-M2-A2-N2-T2-E2-H2, respectively, for the non-G/P 114 genotypes (3).