Murine and related chapparvoviruses are nephro-tropic and produce novel accessory proteins in infected kidneys

Autoři: Quintin Lee aff001;  Matthew P. Padula aff002;  Natalia Pinello aff001;  Simon H. Williams aff003;  Matthew B. O'Rourke aff004;  Marcílio Jorge Fumagalli aff005;  Joseph D. Orkin aff006;  Renhua Song aff001;  Babak Shaban aff008;  Ori Brenner aff009;  John E. Pimanda aff010;  Wolfgang Weninger aff001;  William Marciel de Souza aff005;  Amanda D. Melin aff006;  Justin J.-L. Wong aff001;  Marcus J. Crim aff013;  Sébastien Monette aff014;  Ben Roediger aff001;  Christopher J. Jolly aff010
Působiště autorů: Centenary Institute, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia aff001;  Proteomics Core Facility, University of Technology Sydney, Sydney, NSW, Australia aff002;  Center for Infection & Immunity, Mailman School of Public Health, Columbia University, New York, NY, United States of America aff003;  Kolling Institute of Medical Research, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, Australia aff004;  Virology Research Center, School of Medicine of Ribeirão Preto of the University of São Paulo, Ribeirão Preto, Brazil aff005;  Institut de Biologia Evolutiva, CSIC-Universitat Pompeu Fabra, Barcelona, Spain aff006;  Department of Anthropology and Archaeology, University of Calgary, Alberta, Canada aff007;  Melbourne Integrative Genomics, University of Melbourne, Melbourne, Victoria, Australia aff008;  Department of Veterinary Resources, Weizmann Institute of Science, Rehovot, Israel aff009;  Lowy Cancer Research Centre, University of New South Wales Sydney, Sydney, NSW, Australia aff010;  Department of Dermatology, Medical University of Vienna, Vienna, Austria aff011;  Department of Medical Genetics and Alberta Children’s Hospital Research Institute, Cumming School of Medicine, University of Calgary, Alberta, Canada aff012;  Microbiology and Aquatic Diagnostics, IDEXX BioAnalytics, Discovery Drive, Columbia, MO, United States of America aff013;  Laboratory of Comparative Pathology, Center of Comparative Medicine and Pathology, Memorial Sloan Kettering Cancer Center, The Rockefeller University, Weill Cornell Medicine, New York, NY, United States of America aff014;  Autoimmunity, Transplantation, Inflammation (ATI) Disease Area, Novartis Institutes for Biomedical Research, Basel, Switzerland aff015
Vyšlo v časopise: Murine and related chapparvoviruses are nephro-tropic and produce novel accessory proteins in infected kidneys. PLoS Pathog 16(1): e32767. doi:10.1371/journal.ppat.1008262
Kategorie: Research Article


Mouse kidney parvovirus (MKPV) is a member of the provisional genus Chapparvovirus that causes renal disease in immune-compromised mice, with a disease course reminiscent of polyomavirus-associated nephropathy in immune-suppressed kidney transplant patients. Here we map four major MKPV transcripts, created by alternative splicing, to a common initiator region, and use mass spectrometry to identify “p10” and “p15” as novel chapparvovirus accessory proteins produced in MKPV-infected kidneys. p15 and the splicing-dependent putative accessory protein NS2 are conserved in all near-complete amniote chapparvovirus genomes currently available (from mammals, birds and a reptile). In contrast, p10 may be encoded only by viruses with >60% amino acid identity to MKPV. We show that MKPV is kidney-tropic and that the bat chapparvovirus DrPV-1 and a non-human primate chapparvovirus, CKPV, are also found in the kidneys of their hosts. We propose, therefore, that many mammal chapparvoviruses are likely to be nephrotropic.

Klíčová slova:

Bird genomics – Gene prediction – Introns – Kidneys – Mammalian genomics – Parvoviruses – Polymerase chain reaction – Polyadenylation


1. Cotmore SF, Tattersall P. Parvoviruses: Small Does Not Mean Simple. Annu Rev Virol. 2014;1(1):517–37. doi: 10.1146/annurev-virology-031413-085444 26958732

2. Stutika C, Gogol-Döring A, Botschen L, Mietzsch M, Weger S, Feldkamp M, et al. A Comprehensive RNA Sequencing Analysis of the Adeno-Associated Virus (AAV) Type 2 Transcriptome Reveals Novel AAV Transcripts, Splice Variants, and Derived Proteins. J Virol. 2016;90(3):1278–89. doi: 10.1128/JVI.02750-15 26559843

3. Cotmore SF, Agbandje-McKenna M, Canuti M, Chiorini JA, Eis-Hubinger AM, Hughes J, et al. ICTV Virus Taxonomy Profile: Parvoviridae. J Gen Virol. 2019;100(3):367–368. doi: 10.1099/jgv.0.001212 30672729

4. Lukashov VV, Goudsmit J. Evolutionary relationships among parvoviruses: virus-host coevolution among autonomous primate parvoviruses and links between adeno-associated and avian parvoviruses. J Virol. 2001;75(6):2729–40. doi: 10.1128/JVI.75.6.2729-2740.2001 11222696

5. Nandi S, Kumar M. Canine parvovirus: current perspective. Indian J Virol. 2010;21(1):31–44. doi: 10.1007/s13337-010-0007-y 23637476

6. Meszaros I, Olasz F, Csagola A, Tijssen P, Zadori Z. Biology of Porcine Parvovirus (Ungulate parvovirus 1). Viruses. 2017;9(12):E393. doi: 10.3390/v9120393 29261104

7. Serjeant GR, Topley JM, Mason K, Serjeant BE, Pattison JR, Jones SE, et al. Outbreak of aplastic crises in sickle cell anaemia associated with parvovirus-like agent. Lancet. 1981;2(8247):595–7. doi: 10.1016/s0140-6736(81)92739-2 6116082

8. Logan GJ, Dane AP, Hallwirth CV, Smyth CM, Wilkie EE, Amaya AK, et al. Identification of liver-specific enhancer-promoter activity in the 3' untranslated region of the wild-type AAV2 genome. Nat Genet. 2017;49(8):1267–73. doi: 10.1038/ng.3893 28628105

9. Roediger B, Lee Q, Tikoo S, Cobbin JCA, Henderson JM, Jormakka M, et al. An Atypical Parvovirus Drives Chronic Tubulointerstitial Nephropathy and Kidney Fibrosis. Cell. 2018;175(2):530–43. doi: 10.1016/j.cell.2018.08.013 30220458

10. Williams SH, Che X, Garcia JA, Klena JD, Lee B, Muller D, et al. Viral Diversity of House Mice in New York City. MBio. 2018;9(2):e01354–17. doi: 10.1128/mBio.01354-17 29666290

11. Palinski RM, Mitra N, Hause BM. Discovery of a novel Parvovirinae virus, porcine parvovirus 7, by metagenomic sequencing of porcine rectal swabs. Virus Genes. 2016;52(4):564–7. doi: 10.1007/s11262-016-1322-1 26995221

12. Baker KS, Leggett RM, Bexfield NH, Alston M, Daly G, Todd S, et al. Metagenomic study of the viruses of African straw-coloured fruit bats: detection of a chiropteran poxvirus and isolation of a novel adenovirus. Virology. 2013;441(2):95–106. doi: 10.1016/j.virol.2013.03.014 23562481

13. Reuter G, Boros A, Delwart E, Pankovics P. Novel circular single-stranded DNA virus from turkey faeces. Arch Virol. 2014;159(8):2161–4. doi: 10.1007/s00705-014-2025-3 24562429

14. de Souza WM, Romeiro MF, Fumagalli MJ, Modha S, de Araujo J, Queiroz LH, et al. Chapparvoviruses occur in at least three vertebrate classes and have a broad biogeographic distribution. J Gen Virol. 2017;98(2):225–9. doi: 10.1099/jgv.0.000671 28284244

15. Chong R, Shi M, Grueber CE, Holmes EC, Hogg CJ, Belov K, et al. Fecal Viral Diversity of Captive and Wild Tasmanian Devils Characterized Using Virion-Enriched Metagenomics and Metatranscriptomics. J Virol. 2019;93(11):e00205–19. doi: 10.1128/JVI.00205-19 30867308

16. Penzes JJ, de Souza WM, Agbandje-McKenna M, Gifford RJ. An Ancient Lineage of Highly Divergent Parvoviruses Infects both Vertebrate and Invertebrate Hosts. Viruses. 2019;11(6):E525. doi: 10.3390/v11060525 31174309

17. Fahsbender E, Altan E, Seguin MA, Young P, Estrada M, Leutenegger C, et al. Chapparvovirus DNA Found in 4% of Dogs with Diarrhea. Viruses. 2019;11(5):E398. doi: 10.3390/v11050398 31035625

18. Sawaswong V, Fahsbender E, Altan E, Kemthong T, Deng X, Malaivijitnond S, et al. High Diversity and Novel Enteric Viruses in Fecal Viromes of Healthy Wild and Captive Thai Cynomolgus Macaques (Macaca fascicularis). Viruses. 2019;11(10):971.

19. Orkin JD, de Manuel M, Krawetz R, del Campo J, Fontsere C, Kuderna LFK, et al. Unbiased whole genomes from mammalian feces using fluorescence-activated cell sorting. bioRxiv. 2018:366112.

20. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics. 2009;25(16):2078–9. doi: 10.1093/bioinformatics/btp352 19505943

21. Reese MG, Eeckman FH, Kulp D, Haussler D. Improved Splice Site Detection in Genie. J Comput Biol. 1997;4(3):311–23. doi: 10.1089/cmb.1997.4.311 9278062

22. Spanopoulou E, Roman CA, Corcoran LM, Schlissel MS, Silver DP, Nemazee D, et al. Functional immunoglobulin transgenes guide ordered B-cell differentiation in Rag-1-deficient mice. Genes Dev. 1994;8(9):1030–42. doi: 10.1101/gad.8.9.1030 7926785

23. Mombaerts P, Iacomini J, Johnson RS, Herrup K, Tonegawa S, Papaioannou VE. RAG-1-deficient mice have no mature B and T lymphocytes. Cell. 1992;68:869–77. doi: 10.1016/0092-8674(92)90030-g 1547488

24. Gabriel SI, Stevens MI, Mathias MdL, Searle JB. Of Mice and ‘Convicts’: Origin of the Australian House Mouse, Mus musculus. PLOS ONE. 2011;6(12):e28622. doi: 10.1371/journal.pone.0028622 22174847

25. Smith AL, Singleton GR, Hansen GM, Shellam G. A serologic survey for viruses and Mycoplasma pulmonis among wild house mice (Mus domesticus) in southeastern Australia. J Wildl Dis. 1993;29(2):219–29. doi: 10.7589/0090-3558-29.2.219 8487371

26. Breed B, Ford F. Native Mice and Rats. Collingwood, Victoria, Australia: CSIRO Publishing; 2007. 185 p.

27. Notredame C, Higgins DG, Heringa J. T-Coffee: A novel method for fast and accurate multiple sequence alignment. J Mol Biol. 2000;302(1):205–17. doi: 10.1006/jmbi.2000.4042 10964570

28. Besch-Williford C, Pesavento P, Hamilton S, Bauer B, Kapusinszky B, Phan T, et al. A Naturally Transmitted Epitheliotropic Polyomavirus Pathogenic in Immunodeficient Rats: Characterization, Transmission, and Preliminary Epidemiologic Studies. Toxicol Pathol. 2017;45(5):593–603. doi: 10.1177/0192623317723541 28782456

29. Yang C, Bolotin E, Jiang T, Sladek FM, Martinez E. Prevalence of the initiator over the TATA box in human and yeast genes and identification of DNA motifs enriched in human TATA-less core promoters. Gene. 2007;389(1):52–65. doi: 10.1016/j.gene.2006.09.029 17123746

30. Vo Ngoc L, Cassidy CJ, Huang CY, Duttke SH, Kadonaga JT. The human initiator is a distinct and abundant element that is precisely positioned in focused core promoters. Genes Dev. 2017;31(1):6–11. doi: 10.1101/gad.293837.116 28108474

31. Ganesan LP, Mohanty S, Kim J, Clark KR, Robinson JM, Anderson CL. Rapid and efficient clearance of blood-borne virus by liver sinusoidal endothelium. PLoS Pathog. 2011;7(9):e1002281. doi: 10.1371/journal.ppat.1002281 21980295

32. Lisowski L, Dane AP, Chu K, Zhang Y, Cunningham SC, Wilson EM, et al. Selection and evaluation of clinically relevant AAV variants in a xenograft liver model. Nature. 2014;506(7488):382–6. doi: 10.1038/nature12875 24390344

33. Ramos E, Drachenberg CB, Wali R, Hirsch HH. The decade of polyomavirus BK-associated nephropathy: state of affairs. Transplantation. 2009;87(5):621–30. doi: 10.1097/TP.0b013e318197c17d 19295303

34. Rani A, Ranjan R, McGee HS, Metwally A, Hajjiri Z, Brennan DC, et al. A diverse virome in kidney transplant patients contains multiple viral subtypes with distinct polymorphisms. Sci Rep. 2016;6:33327. doi: 10.1038/srep33327 27633952

35. Edgar RC. MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res. 2004;32(5):1792–7. doi: 10.1093/nar/gkh340 15034147

36. Yang S, Liu Z, Wang Y, Li W, Fu X, Lin Y, et al. A novel rodent Chapparvovirus in feces of wild rats. Virol J. 2016;13:133. doi: 10.1186/s12985-016-0589-0 27473724

37. Yinda CK, Ghogomu SM, Conceicao-Neto N, Beller L, Deboutte W, Vanhulle E, et al. Cameroonian fruit bats harbor divergent viruses, including rotavirus H, bastroviruses, and picobirnaviruses using an alternative genetic code. Virus Evol. 2018;4(1):vey008. doi: 10.1093/ve/vey008 29644096

38. Wang Y, Yang S, Liu D, Zhou C, Li W, Lin Y, et al. The fecal virome of red-crowned cranes. Arch Virol. 2018;164(1):3–16. doi: 10.1007/s00705-018-4037-x 30225519

39. Lima DA, Cibulski SP, Tochetto C, Varela APM, Finkler F, Teixeira TF, et al. The intestinal virome of malabsorption syndrome-affected and unaffected broilers through shotgun metagenomics. Virus Res. 2019;261:9–20. doi: 10.1016/j.virusres.2018.12.005 30543873

40. National Health and Medical Research Council. Australian code for the care and use of animals for scientific purposes, 8th edition. Canberra: National Health and Medical Research Council. 2013.

41. Kearse M, Moir R, Wilson A, Stones-Havas S, Cheung M, Sturrock S, et al. Geneious Basic: an integrated and extendable desktop software platform for the organization and analysis of sequence data. Bioinformatics. 2012;28(12):1647–9. doi: 10.1093/bioinformatics/bts199 22543367

42. Tamura K, Stecher G, Peterson D, Filipski A, Kumar S. MEGA6: Molecular Evolutionary Genetics Analysis version 6.0. Mol Biol Evol. 2013;30(12):2725–9. doi: 10.1093/molbev/mst197 24132122

43. Tamura K. Estimation of the number of nucleotide substitutions when there are strong transition-transversion and G+C-content biases. Mol Biol Evol. 1992;9(4):678–87. doi: 10.1093/oxfordjournals.molbev.a040752 1630306

44. Gnerre S, MacCallum I, Przybylski D, Ribeiro FJ, Burton JN, Walker BJ, et al. High-quality draft assemblies of mammalian genomes from massively parallel sequence data. Proc Nat Acad Sci. 2011;108(4):1513–8. doi: 10.1073/pnas.1017351108 21187386

45. Goldstein LD, Cao Y, Pau G, Lawrence M, Wu TD, Seshagiri S, et al. Prediction and Quantification of Splice Events from RNA-Seq Data. PLoS One. 2016;11(5):e0156132. doi: 10.1371/journal.pone.0156132 27218464

Článek vyšel v časopise

PLOS Pathogens

2020 Číslo 1
Nejčtenější tento týden
Nejčtenější v tomto čísle

Zvyšte si kvalifikaci online z pohodlí domova

Důležitost adherence při depresivním onemocnění
nový kurz
Autoři: MUDr. Eliška Bartečková, Ph.D.

Koncepce osteologické péče pro gynekology a praktické lékaře
Autoři: MUDr. František Šenk

Sekvenční léčba schizofrenie
Autoři: MUDr. Jana Hořínková, Ph.D.

Hypertenze a hypercholesterolémie – synergický efekt léčby
Autoři: prof. MUDr. Hana Rosolová, DrSc.

Multidisciplinární zkušenosti u pacientů s diabetem
Autoři: Prof. MUDr. Martin Haluzík, DrSc., prof. MUDr. Vojtěch Melenovský, CSc., prof. MUDr. Vladimír Tesař, DrSc.

Všechny kurzy
Zapomenuté heslo

Zadejte e-mailovou adresu, se kterou jste vytvářel(a) účet, budou Vám na ni zaslány informace k nastavení nového hesla.


Nemáte účet?  Registrujte se