Chapter 39 : The Human Virome

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The human microbiome is the collection of hundreds of trillions of microorganisms and their genomes that colonize the human body. Recent advances in sequencing technology have allowed these communities and their function to be characterized and defined in detail. While the bacterial members of the microbiome have received the bulk of the attention, the viral members, the human virome, promise to be no less important. This chapter describes these recent advances in the methods for metagenomic studies, highlights key early findings, and looks ahead to the remaining challenges to implementing viral metagenomics and human virome techniques in the clinical setting for diagnostic purposes.

Citation: Ross M, Ajami N, Petrosino J. 2016. The Human Virome, p 527-544. In Loeffelholz M, Hodinka R, Young S, Pinsky B (ed), Clinical Virology Manual, Fifth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555819156.ch39
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1. Subramanian S, Blanton LV, Frese SA, Charbonneau M, Mills DA, Gordon JI . 2015. Cultivating healthy growth and nutrition through the gut microbiota. Cell 161 : 36 48.[PubMed]
2. Weyrich LS, Dixit S, Farrer AG, Cooper AJ, Cooper AJ . 2015. The skin microbiome: Associations between altered microbial communities and disease. Australas J Dermatol; Available from: http://www.ncbi.nlm.nih.gov/pubmed/25715969.
3. Witkin SS . 2015. The vaginal microbiome, vaginal anti-microbial defence mechanisms and the clinical challenge of reducing infection-related preterm birth. BJOG 122 : 213 218.[PubMed]
4. Madsen KL, Doyle JS, Jewell LD, Tavernini MM, Fedorak RN . 1999. Lactobacillus species prevents colitis in interleukin 10 gene-deficient mice. Gastroenterology 116 : 1107 1114.[PubMed]
5. Turnbaugh PJ, Ley RE, Hamady M, Fraser-Liggett CM, Knight R, Gordon JI . 2007. The human microbiome project. Nature 449 : 804 810.[PubMed]
6. Human Microbiome Project Consortium. 2012 . Structure, function and diversity of the healthy human microbiome. Nature 486 : 207214.
7. Duerkop BA, Hooper LV . 2013. Resident viruses and their interactions with the immune system. Nat Immunol 14 : 654 659.[PubMed]
8. Fouhy F, Ross RP, Fitzgerald GF, Stanton C, Cotter PD . 2012. Composition of the early intestinal microbiota: knowledge, knowledge gaps and the use of high-throughput sequencing to address these gaps. Gut Microbes 3 : 203 220.[PubMed]
9. Corfe BM, Harden CJ, Bull M, Garaiova I . 2015. The multifactorial interplay of diet, the microbiome and appetite control: current knowledge and future challenges. Proc Nutr Soc 74 : 235 244.[PubMed]
10. Margulies M, Egholm M, Altman WE, Attiya S, Bader JS, Bemben LA, Berka J, Braverman MS, Chen YJ, Chen Z , , et al . 2005. Genome sequencing in microfabricated high-density picolitre reactors. Nature 437: 376 380.
11. Haiser HJ, Turnbaugh PJ . 2013. Developing a metagenomic view of xenobiotic metabolism. Pharmacol Res 69 : 21 31.[PubMed]
12. Saha JR, Butler VP Jr, Neu HC, Lindenbaum J . 1983. Digoxin-inactivating bacteria: identification in human gut flora. Science 220 : 325 327.
13. Niehues M, Hensel A . 2009. In-vitro interaction of L-dopa with bacterial adhesins of Helicobacter pylori: an explanation for clinicial differences in bioavailability? J Pharm Pharmacol 61 : 1303 1307.[PubMed]
14. Esber A, Vicetti Miguel RD, Cherpes TL, Klebanoff MA, Gallo MF, Turner AN . 2015. Risk of bacterial vaginosis among women with herpes simplex virus type 2 infection: A systematic review and meta-analysis. J Infect Dis 212 : 8 17.[PubMed]
15. Aleandri M, Conte MP, Simonetti G, Panella S, Celestino I, Checconi P, Marazzato M, Longhi C, Goldoni P, Nicoletti M, Barnich N, Palamara AT, Schippa S, Nencioni L . 2015. Influenza A virus infection of intestinal epithelial cells enhances the adhesion ability of Crohn's disease associated Escherichia coli strains. PLoS One 10 : e0117005.[PubMed]
16. Uchiyama R, Chassaing B, Zhang B, Gewirtz AT . 2014. Antibiotic treatment suppresses rotavirus infection and enhances specific humoral immunity. J Infect Dis 210 : 171 182.[PubMed]
17. Woo PCY, Lau SKP, Teng JLL, Tse H, Yuen KY . 2008. Then and now: use of 16S rDNA gene sequencing for bacterial identification and discovery of novel bacteria in clinical microbiology laboratories. Clin Microbiol Infect 14 : 908 934.[PubMed]
18. Breitbart M, Miyake JH, Rohwer F . 2004. Global distribution of nearly identical phage-encoded DNA sequences. FEMS Microbiol Lett 236 : 249 256.[PubMed]
19. Hambly E, Tétart F, Desplats C, Wilson WH, Krisch HM, Mann NH . 2001. A conserved genetic module that encodes the major virion components in both the coliphage T4 and the marine cyanophage S-PM2. Proc Natl Acad Sci USA 98 : 11411 11416.[PubMed]
20. Suttle CA . 2005. Viruses in the sea. Nature 437 : 356 361.[PubMed]
21. Breitbart M, Hewson I, Felts B, Mahaffy JM, Nulton J, Salamon P, Rohwer F . 2003. Metagenomic analyses of an uncultured viral community from human feces. J Bacteriol 185 : 6220 6223.[PubMed]
22. Delwart E . 2013. A roadmap to the human virome. PLoS Pathog 9 : e1003146.[PubMed]
23. Lecuit M, Eloit M . 2013. The human virome: new tools and concepts. Trends Microbiol 21 : 510 515.[PubMed]
24. Breitbart M, Salamon P, Andresen B, Mahaffy JM, Segall AM, Mead D, Azam F, Rohwer F . 2002. Genomic analysis of uncultured marine viral communities. Proc Natl Acad Sci USA 99 : 14250 14255.[PubMed]
25. Grard G, Fair JN, Lee D, Slikas E, Steffen I, Muyembe JJ, Sittler T, Veeraraghavan N, Ruby JG, Wang C, Makuwa M, Mulembakani P, Tesh RB, Mazet J, Rimoin AW, Taylor T, Schneider BS, Simmons G, Delwart E, Wolfe ND, Chiu CY, Leroy EM . 2012. A novel rhabdovirus associated with acute hemorrhagic fever in central Africa. PLoS Pathog 8 : e1002924.[PubMed]
26. Lipkin WI, Firth C . 2013. Viral surveillance and discovery. Curr Opin Virol 3 : 199 204.[PubMed]
27. Tan le V, van Doorn HR, Nghia HD, Chau TT, Tu le TP, de Vries M , , et al . 2013. Identification of a new cyclovirus in cerebrospinal fluid of patients with acute central nervous system infections. MBio 4: e00231 13.
28. Wylie TN, Wylie KM, Herter BN, Storch GA . 2015. Enhanced virome sequencing through solution-based capture enrichment. Genome Res 25: 1910 1920.
29. Briese T, Kapoor A, Mishra N, Jain K, Kumar A, Jabado OJ, Lipkin WI . 2015. Virome capture sequencing enables sensitive viral diagnosis and comprehensive virome analysis. MBio 6 : e01491 e15.[PubMed]
30. Breitbart M, Haynes M, Kelley S, Angly F, Edwards RA, Felts B, Mahaffy JM, Mueller J, Nulton J, Rayhawk S, Rodriguez-Brito B, Salamon P, Rohwer F . 2008. Viral diversity and dynamics in an infant gut. Res Microbiol 159 : 367 373.[PubMed]
31. Kim MS, Park EJ, Roh SW, Bae JW . 2011. Diversity and abundance of single-stranded DNA viruses in human feces. Appl Environ Microbiol 77 : 8062 8070.[PubMed]
32. Minot S, Grunberg S, Wu GD, Lewis JD, Bushman FD . 2012. Hypervariable loci in the human gut virome. Proc Natl Acad Sci USA 109 : 3962 3966.[PubMed]
33. Minot S, Sinha R, Chen J, Li H, Keilbaugh SA, Wu GD, Lewis JD, Bushman FD . 2011. The human gut virome: inter-individual variation and dynamic response to diet. Genome Res 21 : 1616 1625.[PubMed]
34. Reyes A, Haynes M, Hanson N, Angly FE, Heath AC, Rohwer F, Gordon JI . 2010. Viruses in the faecal microbiota of monozygotic twins and their mothers. Nature 466 : 334 338.[PubMed]
35. Zhang T, Breitbart M, Lee WH, Run JQ, Wei CL, Soh SW, Hibberd ML, Liu ET, Rohwer F, Ruan Y . 2006. RNA viral community in human feces: prevalence of plant pathogenic viruses. PLoS Biol 4 : e3.[PubMed]
36. Foxman EF, Iwasaki A . 2011. Genome-virome interactions: examining the role of common viral infections in complex disease. Nat Rev Microbiol 9 : 254 264.[PubMed]
37. Stelekati E, Wherry EJ . 2012. Chronic bystander infections and immunity to unrelated antigens. Cell Host Microbe 12 : 458 469.[PubMed]
38. Mills S, Shanahan F, Stanton C, Hill C, Coffey A, Ross RP . 2013. Movers and shakers: influence of bacteriophages in shaping the mammalian gut microbiota. Gut Microbes 4 : 4 16. t[PubMed]
39. Reyes A, Semenkovich NP, Whiteson K, Rohwer F, Gordon JI . 2012. Going viral: next-generation sequencing applied to phage populations in the human gut. Nat Rev Microbiol 10 : 607 617.[PubMed]
40. Rohwer F, Thurber RV . 2009. Viruses manipulate the marine environment. Nature 459 : 207 212.
41. Koonin EV, Dolja VV, Krupovic M . 2015. Origins and evolution of viruses of eukaryotes: the ultimate modularity. Virology 479–480 : 2 25.[PubMed]
42. Sime-Ngando T . 2014. Environmental bacteriophages: viruses of microbes in aquatic ecosystems. Front Microbiol 5 : 355.[PubMed]
43. Canchaya C, Fournous G, Chibani-Chennoufi S, Dillmann ML, Brüssow H . 2003. Phage as agents of lateral gene transfer. Curr Opin Microbiol 6 : 417 424.[PubMed]
44. Kristensen DM, Mushegian AR, Dolja VV, Koonin EV . 2010. New dimensions of the virus world discovered through metagenomics. Trends Microbiol 18 : 11 19.[PubMed]
45. Brüssow H, Canchaya C, Hardt W-D . 2004. Phages and the evolution of bacterial pathogens: from genomic rearrangements to lysogenic conversion. Microbiol Mol Biol Rev 68: 560 602.
46. Busby B, Kristensen DM, Koonin EV . 2013. Contribution of phage-derived genomic islands to the virulence of facultative bacterial pathogens. Environ Microbiol 15 : 307 312.[PubMed]
47. Carrolo M, Frias MJ, Pinto FR, Melo-Cristino J, Ramirez M . 2010. Prophage spontaneous activation promotes DNA release enhancing biofilm formation in Streptococcus pneumoniae. PLoS One 5 : e15678.[PubMed]
48. Duerkop BA, Clements CV, Rollins D, Rodrigues JLM, Hooper LV . 2012. A composite bacteriophage alters colonization by an intestinal commensal bacterium. Proc Natl Acad Sci USA 109 : 17621 17626.[PubMed]
49. Wang X, Kim Y, Wood TK . 2009. Control and benefits of CP4-57 prophage excision in Escherichia coli biofilms. ISME J 3 : 1164 1179.[PubMed]
50. Willner D, Furlan M, Schmieder R, Grasis JA, Pride DT, Relman DA , , et al . 2011. Metagenomic detection of phage-encoded platelet-binding factors in the human oral cavity. Proc Natl Acad Sci USA 108 ( Suppl 1): 4547 53.
51. Górski A, Wazna E, Da̧browska BW, Da̧browska K, Switała-Jeleń K, Miȩdzybrodzki R . 2006. Bacteriophage translocation. FEMS Immunol Med Microbiol 46 : 313 319.[PubMed]
52. Ventura M, Canchaya C, Pridmore D, Berger B, Brüssow H . 2003. Integration and distribution of Lactobacillus johnsonii prophages. J Bacteriol 185 : 4603 4608.[PubMed]
53. Canchaya C, Desiere F, McShan WM, Ferretti JJ, Parkhill J, Brüssow H . 2002. Genome analysis of an inducible prophage and prophage remnants integrated in the Streptococcus pyogenes strain SF370. Virology 302 : 245 258.[PubMed]
54. Van Sluys MA . , et al . 2003. Comparative analyses of the complete genome sequences of Pierce's disease and citrus variegated chlorosis strains of Xylella fastidiosa. J Bacteriol 185 : 1018 1026.[PubMed]
55. Coleman D, Knights J, Russell R, Shanley D, Birkbeck TH, Dougan G, Charles I . 1991. Insertional inactivation of the Staphylococcus aureus beta-toxin by bacteriophage phi 13 occurs by site- and orientation-specific integration of the phi 13 genome. Mol Microbiol 5 : 933 939.[PubMed]
56. Bossi L, Fuentes JA, Mora G, Figueroa-Bossi N . 2003. Prophage contribution to bacterial population dynamics. J Bacteriol 185 : 6467 6471.[PubMed]
57. Lin L, Bitner R, Edlin G . 1977. Increased reproductive fitness of Escherichia coli lambda lysogens. J Virol 21 : 554 559.[PubMed]
58. Burke J, Schneider D, Westpheling J . 2001. Generalized transduction in Streptomyces coelicolor. Proc Natl Acad Sci USA 98 : 6289 6294.[PubMed]
59. Hodgson DA . 2000. Generalized transduction of serotype 1/2 and serotype 4b strains of Listeria monocytogenes. Mol Microbiol 35 : 312 323.[PubMed]
60. Schicklmaier P, Schmieger H . 1995. Frequency of generalized transducing phages in natural isolates of the Salmonella typhimurium complex. Appl Environ Microbiol 61 : 1637 1640.[PubMed]
61. Allen HK, Looft T, Bayles DO, Humphrey S, Levine UY, Alt D, Stanton TB . 2011. Antibiotics in feed induce prophages in swine fecal microbiomes. MBio 2 : e00260- 11.[PubMed]
62. Amit-Romach E, Uni Z, Reifen R . 2008. Therapeutic potential of two probiotics in inflammatory bowel disease as observed in the trinitrobenzene sulfonic acid model of colitis. Dis Colon Rectum 51 : 1828 1836.[PubMed]
63. Ma D, Forsythe P, Bienenstock J . 2004. Live Lactobacillus rhamnosus [corrected] is essential for the inhibitory effect on tumor necrosis factor alpha-induced interleukin-8 expression. Infect Immun 72 : 5308 5314.[PubMed]
64. Schultz M, Veltkamp C, Dieleman LA, Grenther WB, Wyrick PB, Tonkonogy SL, Sartor RB . 2002. Lactobacillus plantarum 299V in the treatment and prevention of spontaneous colitis in interleukin-10-deficient mice. Inflamm Bowel Dis 8 : 71 80.[PubMed]
65. Cadwell K . 2015. Expanding the role of the virome: commensalism in the gut. J Virol 89 : 1951 1953.
66. Oldstone MB . 1988. Prevention of type I diabetes in nonobese diabetic mice by virus infection. Science 239: 500 502.
67. Colson P, Richet H, Desnues C, Balique F, Moal V, Grob JJ, Berbis P, Lecoq H, Harlé JR, Berland Y, Raoult D . 2010. Pepper mild mottle virus, a plant virus associated with specific immune responses, fever, abdominal pains, and pruritus in humans. PLoS One 5 : e10041. Internet[PubMed]
68. Virgin HW . 2014. The virome in mammalian physiology and disease. Cell 157 : 142 150.[PubMed]
69. Virgin HW, Wherry EJ, Ahmed R . 2009. Redefining chronic viral infection. Cell 138 : 30 50.[PubMed]
70. zur Hausen H . 2008. Novel human polyomaviruses—re-emergence of a well known virus family as possible human carcinogens. Int J Cancer 123 : 247 250.[PubMed]
71. Ninomiya M, Takahashi M, Nishizawa T, Shimosegawa T, Okamoto H . 2008. Development of PCR assays with nested primers specific for differential detection of three human anelloviruses and early acquisition of dual or triple infection during infancy. J Clin Microbiol 46 : 507 514.[PubMed]
72. Spandole S, Cimponeriu D, Berca LM, Mihăescu G . 2015. Human anelloviruses: an update of molecular, epidemiological and clinical aspects. Arch Virol 160 : 893 908.[PubMed]
73. Cibulski SP, Teixeira TF, de Sales Lima FE, do Santos HF, Franco AC, Roehe PM . 2014. A novel anelloviridae species detected in Tadarida brasiliensis bats: First sequence of a chiropteran anellovirus. Genome Announc 2 : e01028- 14.[PubMed]
74. Mi Z, Yuan X, Pei G, Wang W, An X, Zhang Z, Huang Y, Peng F, Li S, Bai C, Tong Y . 2014. High-throughput sequencing exclusively identified a novel Torque teno virus genotype in serum of a patient with fatal fever. Virol Sin 29 : 112 118.[PubMed]
75. Nishiyama S, Dutia BM, Stewart JP, Meredith AL, Shaw DJ, Simmonds P, Sharp CP . 2014. Identification of novel anelloviruses with broad diversity in UK rodents. J Gen Virol 95 : 1544 1553.[PubMed]
76. Peng YH, Nishizawa T, Takahashi M, Ishikawa T, Yoshikawa A, Okamoto H . 2002. Analysis of the entire genomes of thirteen TT virus variants classifiable into the fourth and fifth genetic groups, isolated from viremic infants. Arch Virol 147 : 21 41.[PubMed]
77. Ninomiya M, Nishizawa T, Takahashi M, Lorenzo FR, Shimosegawa T, Okamoto H . 2007. Identification and genomic characterization of a novel human torque teno virus of 3.2 kb. J Gen Virol 88 : 1939 1944.[PubMed]
78. Okamoto H, Nishizawa T, Takahashi M, Tawara A, Peng Y, Kishimoto J, Wang Y . 2001. Genomic and evolutionary characterization of TT virus (TTV) in tupaias and comparison with species-specific TTVs in humans and non-human primates. J Gen Virol 82 : 2041 2050.[PubMed]
79. de Oliveira JC, Nasser TF, Oda JM, Aoki MN, Carneiro JL, Barbosa DS, Reiche EM, Watanabe MA . 2008. Detection of TTV in peripheral blood cells from patients with altered ALT and AST levels. New Microbiol 31 : 195 201.[PubMed]
80. Hussain T, Manzoor S, Waheed Y, Tariq H, Hanif K . 2012. Phylogenetic analysis of Torque Teno Virus genome from Pakistani isolate and incidence of co-infection among HBV/HCV infected patients. Virol J 9: 320.
81. Vasilyev EV, Trofimov DY, Tonevitsky AG, Ilinsky VV, Korostin DO, Rebrikov DV . 2009. Torque Teno Virus (TTV) distribution in healthy Russian population. Virol J 6 : 134.[PubMed]
82. Delwart EL . 2007. Viral metagenomics. Rev Med Virol 17 : 115 131.[PubMed]
83. Rosario K, Breitbart M . 2011. Exploring the viral world through metagenomics. Curr Opin Virol 1 : 289 297.[PubMed]

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