The Human Virome

  • Matthew Haynes
  • Forest Rohwer


In this chapter we discuss changing approaches to viral discovery and human health, summarize the current understanding of the human-associated viral community, and review contemporary methods in viral metagenomics. The virome is the community of viruses that populate an organism or ecosystem at any given time. This includes the “core” set of commensal viruses that do not give rise to clinical symptoms or viremia, combined with any acute or persistent infections that may be present. Recent technological advances enable us to sequence viral genomes without culturing or cloning. These methods permit not only the discovery of a wider range of viral pathogens, but also a broader assessment of the human virome in the absence of clinically recognized disease. A new focus in contemporary virology is the natural viral community of the human body. This will provide a background for recognition of emerging and previously unrecognized viruses. It should be possible to detect viral infection before the emergence of symptoms, which will have significant implications for health-care delivery.


Torque Teno Virus Human Microbiome Brucella Melitensis Viral Community Xylella Fastidiosa 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



amplification bias

Inaccurate representation of the true relative abundances of genotypes in a DNA sample has been subjected to nonspecific amplification methods such as MDA or PCR.


(Basic Local Alignment Search Tool) An algorithm used to search nucleic acid and protein databases for sequences similar to a query sequence (McGinnis and Madden, 2004).


A form of symbiosis that benefits one partner while providing no apparent benefit to the other.


A set of interacting populations in an ecosystem.


A measure of the range of variation in a community, frequently represented as a combination of richness (number of variants) and evenness (skewness of the distribution).


PCR performed in a water-in-oil emulsion, so that each micelle functions as a microreactor containing a single amplicon.


An index of the skewness of variation: an evenness value close to 0 implies that a community is dominated by one or very few members; a value of 1 implies equal abundance of every member.


The nucleic acid (DNA or RNA) that constitutes genetic information from a single organism.


A genetic subtype that can be distinguished in a sample. In practical terms, two sequences will often be considered to legitimately represent the same genotype if they overlap at least 35 base pairs with 98% identity.


(molecular biology) The annealing of complementary single-stranded DNA or RNA.


(multiple displacement amplification) DNA amplification using random primers in an isothermal reaction with a polymerase with helicase activity (Phi29 DNA polymerase), capable of nonspecific replication of double-stranded DNA.


The total genomic nucleic acid (DNA and/or RNA) derived from a community.


A form of symbiosis that benefits both partners.


The total set of members of a genetically distinguishable species or genotypes in a defined biome.

sequence read

A term frequently used to describe a sequence obtained by high-throughput methods


The total number of distinct species or genotypes that can be distinguished in a community.

Shannon–Wiener index

One of the several measures of community diversity. A high value is associated with high richness and evenness values.


A genomic subtype that constitutes a genetic lineage or population that exists in a sample or biome. Due to the genomic plasticity of viruses and microbes it can be challenging to define a species, hence the use of the term genotype in a DNA sample when species definition or identification is problematic.


Any association between two organisms.


The presence of viruses in the blood.


The cumulative viral community in an ecosystem.


  1. Allander T, Tammi MT, Eriksson M, Bjerkner A, Tiveljung-Lindell A, Andersson B (2005) Cloning of a human parvovirus by molecular screening of respiratory tract samples. PNAS 102(36):12891–12896PubMedCentralPubMedCrossRefGoogle Scholar
  2. Angly F, Rodriguez-Brito B, Bangor D, McNairnie P, Salamon P, Felts B, Nulton J, Mahaffy J, Rohwer F (2005) PHACCS, an online tool for estimating the structure and diversity of uncultured viral communities using metagenomic information. BMC Bioinformatics 2(6(1)):41CrossRefGoogle Scholar
  3. Angly FE, Felts B, Breitbart M, Salamon P, Edwards RA, Carlson C, Chan AM, Haynes M, Kelley S, Liu H, Mahaffy JM, Mueller JE, Nulton J, Olson R, Parsons R, Rayhawk S, Suttle CA, Rohwer F (2006) The marine viromes of four oceanic regions. PLoS Biol 4(11):2121–2131Google Scholar
  4. Antonsson A, Forslund O, Ekberg H, Sterner G, Hansson BG (2000) The ubiquity and impressive genomic diversity of human skin papillomaviruses suggest a commensalic nature of these viruses. J Virol 74(24):11636–11641PubMedCentralPubMedCrossRefGoogle Scholar
  5. Breitbart M, Rohwer F (2005) Method for discovering novel DNA viruses in blood using viral particle selection and shotgun sequencing. BioTechniques 39:729–736PubMedCrossRefGoogle Scholar
  6. Breitbart M, Rohwer F, Abedon ST (2005) Phage ecology and bacterial pathogenesis. In: Waldor MK, Friedman DI, Adhya SL (eds) Phages: their role in bacterial pathogenesis and biotechnolgy. ASM Press, Washington, DC, pp 66–92Google Scholar
  7. Breitbart M, Haynes M, Kelley S, Angly F, Edwards RA, Felts B, Mahaffy JM, Mueller J, Nultonc J, Rayhawk S, Rodriguez-Brito B, Salamon P, Rohwer F (2008) Viral diversity and dynamics in an infant gut. Res Microbiol 159(5):367–373PubMedCrossRefGoogle Scholar
  8. 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 185:6220–6223PubMedCentralPubMedCrossRefGoogle Scholar
  9. Burge C, Campbell AM, Karlin S (1992) Over- and under-representation of short oligonucleotides in DNA sequences. PNAS 89(4):1358–1362PubMedCentralPubMedCrossRefGoogle Scholar
  10. Chiu CY, Greninger AL, Kanada K, Kwok T, Fischer KF, Runckel C, Louie JK, Glaser CA, Yagi S, Schnurr DP, Haggerty TD, Parsonnet J, Ganem D, DeRisi JL (2008) Identification of cardioviruses related to Theiler’s murine encephalomyelitis virus in human infections. PNAS 105(37):14124–14129PubMedCentralPubMedCrossRefGoogle Scholar
  11. Delwart EL (2007) Viral metagenomics. Rev Med Virol 17(2):115–131PubMedCrossRefGoogle Scholar
  12. Dethlefsen L, McFall-Ngai M, Relman DA (2007) An ecological and evolutionary perspective on human–microbe mutualism and disease. Nature 449:811–818PubMedCrossRefGoogle Scholar
  13. Furlan M (2009) Viral and microbial dynamics in the human respiratory tract. Biology. San Diego State University, San Diego, CAGoogle Scholar
  14. Gill SR, Pop M, DeBoy RT, Eckburg PB, Turnbaugh PJ, Samuel BS, Gordon JI, Relman DA, Fraser-Liggett CM, Nelson KE (2006) Metagenomic analysis of the human distal gut microbiome. Science 312(5778):1355–1359PubMedCentralPubMedCrossRefGoogle Scholar
  15. Grice E, Kong H, Renaud G, Young A, Bouffard G, Blakesley R, Wolfsberg T, Turner M, Segre J (2008) A diversity profile of the human skin microbiota. Genome Res 18(7):1043–1050PubMedCentralPubMedCrossRefGoogle Scholar
  16. Grice E, Kong H, Conlan S, Deming C, Davis J, Young A, Bouffard G, Blakesley R, Murray P, Green E, Turner M, Segre J (2009) Topographical and temporal diversity of the human skin microbiome. Science 324(5931):1190–1192PubMedCentralPubMedCrossRefGoogle Scholar
  17. Harris JK, Groote MAD, Sagel SD, Zemanick ET, Kapsner R, Penvari C, Kaess H, Deterding RR, Accurso FJ, Pace NR (2007) Molecular identification of bacteria in bronchoalveolar lavage fluid from children with cystic fibrosis. PNAS 104(51):20529–20533PubMedCentralPubMedCrossRefGoogle Scholar
  18. Harrison F (2007) Microbial ecology of the cystic fibrosis lung. Microbiology 153(Part 4):917–923PubMedCrossRefGoogle Scholar
  19. Hendrix RW (2005) Bacteriophage evolution and the role of phages in host evolution. In: Waldor MK, Friedman DI, Adhya SL (eds) Phages: their role in bacterial pathogenesis and biotechnology. ASM Press, Washington, DC, pp 55–65Google Scholar
  20. Hitch G, Pratten J, Taylor PW (2004) Isolation of bacteriophages from the oral cavity. Lett Appl Microbiol 39:215–219PubMedCrossRefGoogle Scholar
  21. Hyman RW, Fukushima M, Diamond L, Kumm J, Giudice LC, Davis RW (2005) Microbes on the human vaginal epithelium. PNAS 102(22):7952–7957PubMedCentralPubMedCrossRefGoogle Scholar
  22. Jones MS, Kapoor A, Lukashov VV, Simmonds P, Hecht F, Delwart E (2005) New DNA viruses identified in patients with acute viral infection syndrome. J Virol 79:8230–8236PubMedCentralPubMedCrossRefGoogle Scholar
  23. Karlin S (1998) Global dinucleotide signatures and analysis of genomic heterogeneity. Curr Opin Microbiol 1(5):598–610PubMedCrossRefGoogle Scholar
  24. Karlin S, Mrazek J, Campbell A (1997) Compositional biases of bacterial genomes and evolutionary implications. J Bacteriol 179(12):3899–3913PubMedCentralPubMedGoogle Scholar
  25. Kistler A, Avila PC, Rouskin S, Wang D, Ward T, Yagi S, Schnurr D, Ganem D, DeRisi JL, Boushey HA (2007) Pan-viral screening of respiratory tract infections in adults with and without asthma reveals unexpected human coronavirus and human rhinovirus diversity. J Infect Dis 196:817–825PubMedCrossRefGoogle Scholar
  26. Ksiazek TG, Erdman D, Goldsmith CS, Zaki SR, Peret T (2003) A novel coronavirus associated with severe acute respiratory syndrome. N Engl J Med 348:1953–1966PubMedCrossRefGoogle Scholar
  27. Kunin V, He S, Warnecke F, Peterson SB, Martin HG, Haynes M, Ivanova N, Blackall LL, Breitbart M, Rohwer F, McMahon KD, Hugenholtz P (2008) A bacterial metapopulation adapts locally to phage predation despite global dispersal. Genome Res 18:293–297Google Scholar
  28. Letarov A, Kulikov E (2009) The bacteriophages in human- and animal body-associated microbial communities. J Appl Microbiol 107(1):1–13PubMedCrossRefGoogle Scholar
  29. Little JW (2005) Lysogeny, prophage induction, and lysogenic conversion. In: Waldor MK, Friedman DI, Adhya SL (eds) Phages: their role in bacterial pathogenesis and biotechnology. ASM Press, Washington, DC, pp 37–54Google Scholar
  30. McGinnis S, Madden TL (2004) BLAST: at the core of a powerful and diverse set of sequence analysis tools. Nucleic Acids Res 32:W20–W25PubMedCentralPubMedCrossRefGoogle Scholar
  31. Meyer F, Paarmann D, D’Souza M, Olson R, Glass EM, Kubal M, Paczian T, Rodriguez A, Stevens R, Wilke A, Wilkening J, Edwards RA (2008) The metagenomics RAST server – a public resource for the automatic phylogenetic and functional analysis of metagenomes. BMC Bioinformatics 9:386PubMedCentralPubMedCrossRefGoogle Scholar
  32. Nakamura S, Yang C-S, Sakon N, Ueda M, Tougan T, Yamashita A, Goto N, Takahashi K, Yasunaga T, Ikuta K, Mizutani T, Okamoto Y, Tagami M, Morita R, Maeda N, Kawai J, Hayashizaki Y, Nagai Y, Horii T, Iida T, Nakaya T (2009) Direct metagenomic detection of viral pathogens in nasal and fecal specimens using an unbiased high-throughput sequencing approach. PLoS One 4(1):e4219 [online only]Google Scholar
  33. Okamoto H (2009) History of discoveries and pathogenicity of TT viruses. Curr Top Microbiol Immunol 331:1–201–220PubMedGoogle Scholar
  34. Relman DA (2002) The human body as microbial observatory. Nat Genet 30:131–133PubMedCrossRefGoogle Scholar
  35. Reyes A, Haynes M, Hanson N, Angly FE, Heath AC, Rohwer F, Gordon J (2009) Phages in the distal human gut. Nature 466:334–338Google Scholar
  36. Rivers TM (1937) Viruses and Koch’s postulates. J Bacteriol 33(1):1–12PubMedCentralPubMedGoogle Scholar
  37. Rodriguez-Mueller B, Li LL, Wegley L, Furlan M, Angly F, Breitbart M, Buchanan J, Desnues C, Dinsdale E, Edwards R, Felts B, Haynes M, Liu H, Lipson D, Mahaffy J, Martin-Cuadrado AB, Mira A, Nulton J, Pasic L, Rayhawk S, Rodriguez-Mueller J, Rodriguez-Valera F, Salamon S, Thingstad TF, Tran T, Willner D, Youle M, Rohwer F (2010) Viral and microbial community dynamics in four aquatic environments. ISME J 4(6):739–751Google Scholar
  38. Rogers GB, Carroll MP, Serisier DJ, Hockey PM, Jones G, Bruce KD (2004) Characterization of bacterial community diversity in cystic fibrosis lung infections by use of 16S ribosomal DNA terminal restriction fragment length polymorphism profiling. J Clin Microbiol 42(11):5176–5183PubMedCentralPubMedCrossRefGoogle Scholar
  39. Rohwer F (2003) Global phage diversity. Cell 113(2):141PubMedCrossRefGoogle Scholar
  40. Savage DC (1977) Microbial ecology of the gastrointestinal tract. Ann Rev Microbiol 31:107–133CrossRefGoogle Scholar
  41. Sharon I, Alperovitch A, Rohwer F, Haynes M, Glaser F, Atamna-Ismaeel N, Pinter RY, Partensky F, Koonin EV, Wolf YI, Nelson N, Béjà O (2009) Photosystem I gene cassettes are present in marine virus genomes. Nature 461:258–262PubMedCrossRefGoogle Scholar
  42. Stapleton JT, Williams CF, Xiang J (2004) GB virus type C: a beneficial infection? J Clin Microbiol 42(9):3915–3919PubMedCentralPubMedCrossRefGoogle Scholar
  43. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, Ley RE, Sogin ML, Jones WJ, Roe BA, Affourtit JP, Egholm M, Henrissat B, Heath AC, Knight R, Gordon JI (2009) A core gut microbiome in obese and lean twins. Nature 457:480–484PubMedCentralPubMedCrossRefGoogle Scholar
  44. Urisman A, Fischer KF, Chiu CY, Kistler AL, Beck S, Wang D, DeRisi JL (2005) E-Predict: a computational strategy for species identification based on observed DNA microarray hybridization patterns. Genome Biol 6: R78 [online only]Google Scholar
  45. Victoria JG, Kapoor A, Li L, Blinkova O, Slikas B, Wang C, Naeem A, Zaidi S, Delwart E (2009) Metagenomic analyses of viruses in stool samples from children with acute flaccid paralysis. J Virol 83:4642–4651PubMedCentralPubMedCrossRefGoogle Scholar
  46. Virgin HW, Wherry EJ, Ahmed R (2009) Redefining chronic viral infection. Cell 138:30–50PubMedCrossRefGoogle Scholar
  47. Wagner PL, Waldor MK (2002) Bacteriophage control of bacterial virulence. Infect Immun 70(8):3985–3993PubMedCentralPubMedCrossRefGoogle Scholar
  48. Wang D, Coscoy L, Zylberberg M, Avila PC, Boushey HA, Ganem D, DeRisi JL (2002) Microarray-based detection and genotyping of viral pathogens. Proc Natl Acad Sci USA 99:15687–15692PubMedCentralPubMedCrossRefGoogle Scholar
  49. Weinbauer MG (2006) Ecology of prokaryotic viruses. FEMS Microbiol Rev 28(2):127–181CrossRefGoogle Scholar
  50. Willner D, Furlan M, Haynes M, Schmieder R, Angly F, Silva J, Tammadoni S, Nosrat B, Conrad D, Rohwer F (2009a) Metagenomic analysis of respiratory tract DNA viral communities in cystic fibrosis and non-cystic fibrosis individuals. PLoS One 4(10):e7370PubMedCentralPubMedCrossRefGoogle Scholar
  51. Willner D, Furlan M, Schmieder R, Grasis J, Pride D, Relman D, Angly FE, McDole T, Mariella R, Rohwer F, Haynes M (2010) Metagenomic detection of phage-encoded platelet-binding factors in the human oral cavity. PNAS Early Edition.Google Scholar
  52. Willner D, Thurber RV, Rohwer F (2009c) Metagenomic signatures of 86 microbial and viral metagenomes. Environ Microbiol 11(7):1752–1766PubMedCrossRefGoogle Scholar
  53. Wilson M (2005) Microbial inhabitants of humans: their ecology and role in health and disease. Cambridge University Press, New York, NYGoogle Scholar
  54. Zhang T, Breitbart M, Lee WH, Run J-Q, Wei CL, Soh SWL, Hibberd ML, Liu ET, Rohwer F, Ruan Y (2005) RNA viral community in human feces: prevalence of plant pathogenic viruses. PLoS Biol 4(1):e3[online only]Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of BiologySan Diego State UniversitySan DiegoUSA

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