The Human Virome
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.
KeywordsTorque Teno Virus Human Microbiome Brucella Melitensis Viral Community Xylella Fastidiosa
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.
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.
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.
- 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
- 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
- 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
- Furlan M (2009) Viral and microbial dynamics in the human respiratory tract. Biology. San Diego State University, San Diego, CAGoogle Scholar
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- 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
- Wilson M (2005) Microbial inhabitants of humans: their ecology and role in health and disease. Cambridge University Press, New York, NYGoogle Scholar
- 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