Abstract
Emerging and re-emerging viruses continue to surface all over the world. Some of these viruses have the potential for rapid and global spread with high morbidity and mortality, such as the SARS coronavirus outbreak. It is extremely urgent and important to identify a novel virus near-instantaneously to develop an active preventive and/or control strategy. As a culture-independent approach, viral metagenomics has been widely used to investigate highly divergent and completely new viruses in humans, animals, and even environmental samples in the past decade. A new model of Koch’s postulates, named the metagenomic Koch’s postulates, has provided guidance for the study of the pathogenicity of novel viruses. This review explains the viral metagenomics strategy for virus discovery and describes viruses discovered in human feces in the past 10 years using this approach. This review also addresses issues related to the metagenomic Koch’s postulates and the challenges for virus discovery in the future.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Fouchier R A, Kuiken T, Schutten M, et al. Aetiology: Koch’s postulates fulfilled for SARS virus. Nature, 2003, 423: 240
Drosten C, Gunther S, Preiser W, et al. Identification of a novel coronavirus in patients with severe acute respiratory syndrome. N Engl J Med, 2003, 348: 1967–1976
Marra M A, Jones S J, Astell C R, et al. The Genome sequence of the SARS-associated coronavirus. Science, 2003, 300: 1399–1404
Peiris J S, Guan Y, Yuen K Y. Severe acute respiratory syndrome. Nat Med, 2004, 10: S88–S97
Rota P A, Oberste M S, Monroe S S, et al. Characterization of a novel coronavirus associated with severe acute respiratory syndrome. Science, 2003, 300: 1394–1399
Reyes G R, Kim J P. Sequence-independent, single-primer amplification (SISPA) of complex DNA populations. Mol Cell Probes, 1991, 5: 473–481
Radford A D, Chapman D, Dixon L, et al. Application of next-generation sequencing technologies in virology. J Gen Virol, 2012, 93: 1853–1868
Margulies M, Egholm M, Altman W E, et al. Genome sequencing in microfabricated high-density picolitre reactors. Nature, 2005, 437: 376–380
Rosario K, Breitbart M. Exploring the viral world through metagenomics. Curr Opin Virol, 2011, 1: 289–297
Mokili J L, Rohwer F, Dutilh B E. Metagenomics and future perspectives in virus discovery. Curr Opin Virol, 2012, 2: 63–77
Delwart E L. Viral metagenomics. Rev Med Virol, 2007, 17: 115–131
Yu X J, Liang M F, Zhang S Y, et al. Fever with thrombocytopenia associated with a novel bunyavirus in China. N Engl J Med, 2011, 364: 1523–1532
Wu Y, Gao G F. Severe fever with thrombocytopenia syndrome virus expands its borders. Emerg Microbes Infect, 2013, in press
Allander T, Tammi M T, Eriksson M, et al. Cloning of a human parvovirus by molecular screening of respiratory tract samples. Proc Natl Acad Sci USA, 2005, 102: 12891–12896
Zaki A M, van Boheemen S, Bestebroer T M, et al. Isolation of a novel coronavirus from a man with pneumonia in Saudi Arabia. N Engl J Med, 2012, 367: 1814–1820
van Boheemen S, de Graaf M, Lauber C, et al. Genomic characterization of a newly discovered coronavirus associated with acute respiratory distress syndrome in humans. MBio, 2012, 3: e00473–12
Chan J F, Li K S, To K K, et al. Is the discovery of the novel human betacoronavirus 2c EMC/2012 (HCoV-EMC) the beginning of another SARS-like pandemic? J Infect, 2012, 65: 477–489
Mullis K, Faloona F, Scharf S, et al. Specific enzymatic amplification of DNA in vitro: the polymerase chain reaction. Cold Spring Harb Symp Quant Biol, 1986, 51(Pt 1): 263–273
Sanger F, Nicklen S, Coulson A R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA, 1977, 74: 5463–5467
Benson D A, Karsch-Mizrachi I, Lipman D J, et al. GenBank. Nucleic Acids Res, 2011, 39: D32–D37
Murray K, Selleck P, Hooper P, et al. A morbillivirus that caused fatal disease in horses and humans. Science, 1995, 268: 94–97
Chua K B, Bellini W J, Rota P A, et al. Nipah virus: a recently emergent deadly paramyxovirus. Science, 2000, 288: 1432–1435
Philbey A W, Kirkland P D, Ross A D, et al. An apparently new virus (family Paramyxoviridae) infectious for pigs, humans, and fruit bats. Emerg Infect Dis, 1998, 4: 269–271
Chua K B, Crameri G, Hyatt A, et al. A previously unknown reovirus of bat origin is associated with an acute respiratory disease in humans. Proc Natl Acad Sci USA, 2007, 104: 11424–11429
Barrette R W, Metwally S A, Rowland J M, et al. Discovery of swine as a host for the Reston ebolavirus. Science, 2009, 325: 204–206
Mokili J L, Rogers M, Carr J K, et al. Identification of a novel clade of human immunodeficiency virus type 1 in Democratic Republic of Congo. AIDS Res Hum Retroviruses, 2002, 18: 817–823
Takemura T, Ekwalanga M, Bikandou B, et al. A novel simian immunodeficiency virus from black mangabey (Lophocebus aterrimus) in the Democratic Republic of Congo. J Gen Virol, 2005, 86: 1967–1971
Barlow K L, Ajao A O, Clewley J P. Characterization of a novel simian immunodeficiency virus (SIVmonNG1) genome sequence from a mona monkey (Cercopithecus mona). J Virol, 2003, 77: 6879–6888
Clewley J P, Lewis J C, Brown D W, et al. A novel simian immunodeficiency virus (SIVdrl) pol sequence from the drill monkey, Mandrillus leucophaeus. J Virol, 1998, 72: 10305–10309
Reyes G R, Purdy M A, Kim J P, et al. Isolation of a cDNA from the virus responsible for enterically transmitted non-A, non-B hepatitis. Science, 1990, 247: 1335–1339
Chou C C, Lee T T, Chen C H, et al. Design of microarray probes for virus identification and detection of emerging viruses at the genus level. BMC Bioinformatics, 2006, 7: 232
Nicholson T L, Kukielka D, Vincent A L, et al. Utility of a panviral microarray for detection of swine respiratory viruses in clinical samples. J Clin Microbiol, 2011, 49: 1542–1548
Yozwiak N L, Skewes-Cox P, Stenglein M D, et al. Virus identification in unknown tropical febrile illness cases using deep sequencing. PLoS Negl Trop Dis, 2012, 6: e1485
Bexfield N, Kellam P. Metagenomics and the molecular identification of novel viruses. Vet J, 2011, 190: 191–198
Finkbeiner S R, Li Y, Ruone S, et al. Identification of a novel astrovirus (astrovirus VA1) associated with an outbreak of acute gastroenteritis. J Virol, 2009, 83: 10836–10839
Allander T, Emerson S U, Engle R E, et al. A virus discovery method incorporating DNase treatment and its application to the identification of two bovine parvovirus species. Proc Natl Acad Sci USA, 2001, 98: 11609–11614
Handelsman J, Rondon M R, Brady S F, et al. Molecular biological access to the chemistry of unknown soil microbes: a new frontier for natural products. Chem Biol, 1998, 5: R245–R249
Riesenfeld C S, Schloss P D, Handelsman J. Metagenomics: genomic analysis of microbial communities. Annu Rev Genet, 2004, 38: 525–552
Schloss P D, Handelsman J. Biotechnological prospects from metagenomics. Curr Opin Biotechnol, 2003, 14: 303–310
Breitbart M, Salamon P, Andresen B, et al. Genomic analysis of uncultured marine viral communities. Proc Natl Acad Sci USA, 2002, 99: 14250–14255
Thurber R V, Haynes M, Breitbart M, et al. Laboratory procedures to generate viral metagenomes. Nat Protoc, 2009, 4: 470–483
Edwards R A, Rodriguez-Brito B, Wegley L, et al. Using pyrosequencing to shed light on deep mine microbial ecology. BMC Genomics, 2006, 7: 57
Breitbart M, Rohwer F. Method for discovering novel DNA viruses in blood using viral particle selection and shotgun sequencing. Biotechniques, 2005, 39: 729–736
Willner D, Furlan M, Schmieder R, et al. Metagenomic detection of phage-encoded platelet-binding factors in the human oral cavity. Proc Natl Acad Sci USA, 2011, 108(Suppl 1): 4547–4553
Endoh D, Mizutani T, Kirisawa R, et al. Species-independent detection of RNA virus by representational difference analysis using non-ribosomal hexanucleotides for reverse transcription. Nucleic Acids Res, 2005, 33: e65
Armour C D, Castle J C, Chen R, et al. Digital transcriptome profiling using selective hexamer priming for cDNA synthesis. Nat Methods, 2009, 6: 647–649
He S, Wurtzel O, Singh K, et al. Validation of two ribosomal RNA removal methods for microbial metatranscriptomics. Nat Methods, 2010, 7: 807–812
Stewart F J, Ottesen E A, DeLong E F. Development and quantitative analyses of a universal rRNA-subtraction protocol for microbial metatranscriptomics. ISME J, 2010, 4: 896–907
Chen Z, Duan X. Ribosomal RNA depletion for massively parallel bacterial RNA-sequencing applications. Methods Mol Biol, 2011, 733: 93–103
Blomstrom A L. Viral metagenomics as an emerging and powerful tool in veterinary medicine. Vet Q, 2011, 31: 107–114
Gilles A, Meglecz E, Pech N, et al. Accuracy and quality assessment of 454 GS-FLX Titanium pyrosequencing. BMC Genomics, 2011, 12: 245
Loman N J, Misra R V, Dallman T J, et al. Performance comparison of benchtop high-throughput sequencing platforms. Nat Biotechnol, 2012, 30: 434–439
Quail M A, Smith M, Coupland P, et al. A tale of three next generation sequencing platforms: comparison of Ion Torrent, Pacific Biosciences and Illumina MiSeq sequencers. BMC Genomics, 2012, 13: 341
Liu L, Li Y, Li S, et al. Comparison of next-generation sequencing systems. J Biomed Biotechnol, 2012, 2012: 251364
Zerbino D R, Birney E. Velvet: algorithms for de novo short read assembly using de Bruijn graphs. Genome Res, 2008, 18: 821–829
Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics, 2009, 25: 1754–1760
Berlin L E, Rorabaugh M L, Heldrich F, et al. Aseptic meningitis in infants <2 years of age: diagnosis and etiology. J Infect Dis, 1993, 168: 888–892
Victoria J G, Kapoor A, Li L, et al. Metagenomic analyses of viruses in stool samples from children with acute flaccid paralysis. J Virol, 2009, 83: 4642–4651
Kapoor A, Victoria J, Simmonds P, et al. A highly prevalent and genetically diversified Picornaviridae genus in South Asian children. Proc Natl Acad Sci USA, 2008, 105: 20482–20487
Holtz L R, Finkbeiner S R, Kirkwood C D, et al. Identification of a novel picornavirus related to cosaviruses in a child with acute diarrhea. Virol J, 2008, 5: 159
Dai X Q, Hua X G, Shan T L, et al. Human cosavirus infections in children in China. J Clin Virol, 2010, 48: 228–229
Khamrin P, Chaimongkol N, Malasao R, et al. Detection and molecular characterization of cosavirus in adults with diarrhea, Thailand. Virus Genes, 2012, 44: 244–246
Kapusinszky B, Phan T G, Kapoor A, et al. Genetic diversity of the genus Cosavirus in the family Picornaviridae: a new species, recombination, and 26 new genotypes. PLoS ONE, 2012, 7: e36685
Stocker A, Souza B F, Ribeiro T C, et al. Cosavirus infection in persons with and without gastroenteritis, Brazil. Emerg Infect Dis, 2012, 18: 656–659
Greninger A L, Runckel C, Chiu C Y, et al. The complete genome of klassevirus—a novel picornavirus in pediatric stool. Virol J, 2009, 6: 82
Li L, Victoria J, Kapoor A, et al. A novel picornavirus associated with gastroenteritis. J Virol, 2009, 83: 12002–12006
Arthur J L, Higgins G D, Davidson G P, et al. A novel bocavirus associated with acute gastroenteritis in Australian children. PLoS Pathog, 2009, 5: e1000391
Kapoor A, Slikas E, Simmonds P, et al. A newly identified bocavirus species in human stool. J Infect Dis, 2009, 199: 196–200
Kapoor A, Simmonds P, Slikas E, et al. Human bocaviruses are highly diverse, dispersed, recombination prone, and prevalent in enteric infections. J Infect Dis, 2010, 201: 1633–1643
Chieochansin T, Kapoor A, Delwart E, et al. Absence of detectable replication of human bocavirus species 2 in respiratory tract. Emerg Infect Dis, 2009, 15: 1503–1505
Chow B D, Ou Z, Esper F P. Newly recognized bocaviruses (HBoV, HBoV2) in children and adults with gastrointestinal illness in the United States. J Clin Virol, 2010, 47: 143–147
Jartti T, Hedman K, Jartti L, et al. Human bocavirus—the first 5 years. Rev Med Virol, 2012, 22: 46–64
Jones M S, Kapoor A, Lukashov V V, et al. New DNA viruses identified in patients with acute viral infection syndrome. J Virol, 2005, 79: 8230–8236
Lau S K, Woo P C, Tse H, et al. Identification of novel porcine and bovine parvoviruses closely related to human parvovirus 4. J Gen Virol, 2008, 89: 1840–1848
Phan T G, Vo N P, Bonkoungou I J, et al. Acute diarrhea in West African children: diverse enteric viruses and a novel parvovirus genus. J Virol, 2012, 86: 11024–11030
Finkbeiner S R, Allred A F, Tarr P I, et al. Metagenomic analysis of human diarrhea: viral detection and discovery. PLoS Pathog, 2008, 4: e1000011
Finkbeiner S R, Kirkwood C D, Wang D. Complete genome sequence of a highly divergent astrovirus isolated from a child with acute diarrhea. Virol J, 2008, 5: 117
Finkbeiner S R, Le B M, Holtz L R, et al. Detection of newly described astrovirus MLB1 in stool samples from children. Emerg Infect Dis, 2009, 15: 441–444
Finkbeiner S R, Li Y, Ruone S, et al. Identification of a novel astrovirus (astrovirus VA1) associated with an outbreak of acute gastroenteritis. J Virol, 2009, 83: 10836–10839
Finkbeiner S R, Holtz L R, Jiang Y, et al. Human stool contains a previously unrecognized diversity of novel astroviruses. Virol J, 2009, 6: 161
Kapoor A, Li L, Victoria J, et al. Multiple novel astrovirus species in human stool. J Gen Virol, 2009, 90: 2965–2972
Allander T, Andreasson K, Gupta S, et al. Identification of a third human polyomavirus. J Virol, 2007, 81: 4130–4136
Gaynor A M, Nissen M D, Whiley D M, et al. Identification of a novel polyomavirus from patients with acute respiratory tract infections. PLoS Pathog, 2007, 3: e64
Feng H, Shuda M, Chang Y, et al. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science, 2008, 319: 1096–1100
Schowalter R M, Pastrana D V, Pumphrey K A, et al. Merkel cell polyomavirus and two previously unknown polyomaviruses are chronically shed from human skin. Cell Host Microbe, 2010, 7: 509–515
Scuda N, Hofmann J, Calvignac-Spencer S, et al. A novel human polyomavirus closely related to the african green monkey-derived lymphotropic polyomavirus. J Virol, 2011, 85: 4586–4590
van der Meijden E, Janssens R W, Lauber C, et al. Discovery of a new human polyomavirus associated with trichodysplasia spinulosa in an immunocompromized patient. PLoS Pathog, 2010, 6: e1001024
Siebrasse E A, Reyes A, Lim E S, et al. Identification of MW polyomavirus, a novel polyomavirus in human stool. J Virol, 2012, 86: 10321–10326
Yu G, Greninger A L, Isa P, et al. Discovery of a novel polyomavirus in acute diarrheal samples from children. PLoS ONE, 2012, 7: e49449
Fringuelli E, Scott A N, Beckett A, et al. Diagnosis of duck circovirus infections by conventional and real-time polymerase chain reaction tests. Avian Pathol, 2005, 34: 495–500
Blinkova O, Victoria J, Li Y, et al. Novel circular DNA viruses in stool samples of wild-living chimpanzees. J Gen Virol, 2010, 91: 74–86
Li L, Kapoor A, Slikas B, et al. Multiple diverse circoviruses infect farm animals and are commonly found in human and chimpanzee feces. J Virol, 2010, 84: 1674–1682
Rijsewijk F A, Dos S H, Teixeira T F, et al. Discovery of a genome of a distant relative of chicken anemia virus reveals a new member of the genus Gyrovirus. Arch Virol, 2011, 156: 1097–1100
Sauvage V, Cheval J, Foulongne V, et al. Identification of the first human gyrovirus, a virus related to chicken anemia virus. J Virol, 2011, 85: 7948–7950
Phan T G, Li L, O’Ryan M G, et al. A third gyrovirus species in human faeces. J Gen Virol, 2012, 93: 1356–1361
Chu D K, Poon L L, Chiu S S, et al. Characterization of a novel gyrovirus in human stool and chicken meat. J Clin Virol, 2012, 55: 209–213
Zhang X, Xie Q, Ji J, et al. Complete genome sequence analysis of a recent chicken anemia virus isolate and comparison with a chicken anemia virus isolate from human fecal samples in China. J Virol, 2012, 86: 10896–10897
Sikorski A, Arguello-Astorga G R, Dayaram A, et al. Discovery of a novel circular single-stranded DNA virus from porcine faeces. Arch Virol, 2013, 158: 283–289
Kim H K, Park S J, Nguyen V G, et al. Identification of a novel single-stranded, circular DNA virus from bovine stool. J Gen Virol, 2012, 93: 635–639
Kosek M, Bern C, Guerrant R L. The global burden of diarrhoeal disease, as estimated from studies published between 1992 and 2000. Bull World Health Organ, 2003, 81: 197–204
O”Ryan M, Prado V, Pickering L K. A millennium update on pediatric diarrheal illness in the developing world. Semin Pediatr Infect Dis, 2005, 16: 125–136
Denno D M, Stapp J R, Boster D R, et al. Etiology of diarrhea in pediatric outpatient settings. Pediatr Infect Dis J, 2005, 24: 142–148
Fredericks D N, Relman D A. Sequence-based identification of microbial pathogens: a reconsideration of Koch’s postulates. Clin Microbiol Rev, 1996, 9: 18–33
Rivers T M. Viruses and Koch’s Postulates. J Bacteriol, 1937, 33: 1–12
Falkow S. Molecular Koch’s postulates applied to microbial pathogenicity. Rev Infect Dis, 1988, 10(Suppl 2): S274–S276
Delwart E. Animal virus discovery: improving animal health, understanding zoonoses, and opportunities for vaccine development. Curr Opin Virol, 2012, 2: 344–352
Hoffmann B, Scheuch M, Hoper D, et al. Novel orthobunyavirus in Cattle, Europe, 2011. Emerg Infect Dis, 2012, 18: 469–472
Garigliany M M, Bayrou C, Kleijnen D, et al. Schmallenberg virus: a new Shamonda/Sathuperi-like virus on the rise in Europe. Antiviral Res, 2012, 95: 82–87
Beer M, Conraths F J, van der Poel W H. ‘Schmallenberg virus’—a novel orthobunyavirus emerging in Europe. Epidemiol Infect, 2013, 141: 1–8
Kilpatrick A M, Randolph S E. Drivers, dynamics, and control of emerging vector-borne zoonotic diseases. Lancet, 2012, 380: 1946–1955
Morse S S, Mazet J A, Woolhouse M, et al. Prediction and prevention of the next pandemic zoonosis. Lancet, 2012, 380: 1956–1965
Karesh W B, Dobson A, Lloyd-Smith J O, et al. Ecology of zoonoses: natural and unnatural histories. Lancet, 2012, 380: 1936–1945
Pickett B E, Greer D S, Zhang Y, et al. Virus pathogen database and analysis resource (ViPR): a comprehensive bioinformatics database and analysis resource for the coronavirus research community. Viruses, 2012, 4: 3209–3226
Pickett B E, Sadat E L, Zhang Y, et al. ViPR: an open bioinformatics database and analysis resource for virology research. Nucleic Acids Res, 2012, 40: D593–D598
Woolhouse M E, Howey R, Gaunt E, et al. Temporal trends in the discovery of human viruses. Proc Biol Sci, 2008, 275: 2111–2115
Author information
Authors and Affiliations
Corresponding author
Additional information
This article is published with open access at Springerlink.com
Rights and permissions
Open Access This article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
About this article
Cite this article
Xie, G., Yu, J. & Duan, Z. New strategy for virus discovery: viruses identified in human feces in the last decade. Sci. China Life Sci. 56, 688–696 (2013). https://doi.org/10.1007/s11427-013-4516-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-013-4516-y