Virome

Last updated

Virome refers to the assemblage of viruses [1] [2] that is often investigated and described by metagenomic sequencing of viral nucleic acids [3] that are found associated with a particular ecosystem, organism or holobiont. The word is frequently used to describe environmental viral shotgun metagenomes. Viruses, including bacteriophages, are found in all environments, and studies of the virome have provided insights into nutrient cycling, [4] [5] development of immunity, [6] and a major source of genes through lysogenic conversion. [7] Also, the human virome has been characterized in nine organs (colon, liver, lung, heart, brain, kidney, skin, blood, hair) of 31 Finnish individuals using qPCR and NGS methodologies. [8]

Contents

History

The first comprehensive studies of viromes were by shotgun community sequencing, [9] which is frequently referred to as metagenomics. In the 2000s, the Rohwer lab sequenced viromes from seawater, [9] [10] marine sediments, [11] adult human stool, [12] infant human stool, [13] soil, [14] and blood. [15] This group also performed the first RNA virome with collaborators from the Genomic Institute of Singapore. [16] From these early works, it was concluded that most of the genomic diversity is contained in the global virome and that most of this diversity remains uncharacterized. [17] This view was supported by individual genomic sequencing project, particularly the mycobacterium phage. [18]

By the late 2010s advances in sequencing technologies have allowed for a deep probing of viromes. [19] The virome of the human gut in particular has gained increased attention as a result of these advancements. [20] [21]

Methods of study

In order to study the virome, virus-like particles are separated from cellular components, usually using a combination of filtration, density centrifugation, and enzymatic treatments to get rid of free nucleic acids. [22] The nucleic acids are then sequenced and analyzed using metagenomic methods. Alternatively, there are recent computational methods that use directly metagenomic assembled sequences to discover viruses. [23]

The Global Ocean Viromes (GOV) is a dataset consisting of deep sequencing from over 150 samples collected across the world's oceans in two survey periods by an international team. [24]

Virus hosts

We can determine the metagenome host from prophage identity sequence. Host virus4.png
We can determine the metagenome host from prophage identity sequence.

Viruses are the most abundant biological entities on Earth, but challenges in detecting, isolating, and classifying unknown viruses have prevented exhaustive surveys of the global virome. [25] Over 5 Tb of metagenomic sequence data were used from 3,042 geographically diverse samples to assess the global distribution, phylogenetic diversity, and host specificity of viruses. [25]

In August 2016, over 125,000 partial DNA viral genomes, including the largest phage yet identified, increased the number of known viral genes by 16-fold. [25] A suite of computational methods was used to identify putative host virus connections. [25] The isolate viral host information was projected onto a group, resulting in host assignments for 2.4% of viral groups. [25]

Then the CRISPR–Cas prokaryotic immune system which holds a "library" of genome fragments from phages (proto-spacers) that have previously infected the host. [25] Spacers from isolate microbial genomes with matches to metagenomic viral contigs (mVCs) were identified for 4.4% of the viral groups and 1.7% of singletons. [25] The hypothesis was explored that viral transfer RNA (tRNA) genes originate from their host. [25]

Viral tRNAs identified in 7.6% of the mVCs were matched to isolate genomes from a single species or genus. [25] The specificity of tRNA-based host viral assignment was confirmed by CRISPR–Cas spacer matches showing a 94% agreement at the genus level. These approaches identified 9,992 putative host–virus associations enabling host assignment to 7.7% of mVCs. [25] The majority of these connections were previously unknown, and include hosts from 16 prokaryotic phyla for which no viruses have previously been identified. [25]

Many viruses specialize in infecting related hosts. [25] Viral generalists that infect hosts across taxonomic orders may exist. [25] Most CRISPR spacer matches were from viral sequences to hosts within one species or genus. [25] Some mVCs were linked to multiple hosts from higher taxa. A viral group composed of macs from human oral samples contained three distinct photo-spacers with nearly exact matches to spacers in Actionbacteria and Bacillota. [25]

Three proto-spacers encoded on mVCs identified in human oral metagenomic samples that were linked to CRISPR spacers from hosts from distinct phyla, Actinomycetes sp. oral taxon 180 (Actinomycetota) and Streptococcus plurextorum DSM 22810 (Bacillota). Host virus2.png
Three proto-spacers encoded on mVCs identified in human oral metagenomic samples that were linked to CRISPR spacers from hosts from distinct phyla, Actinomycetes sp. oral taxon 180 (Actinomycetota) and Streptococcus plurextorum DSM 22810 (Bacillota).
Proportion of 18,470 viral connected with predicted hosts at various taxonomic levels VIRUS HOST.png
Proportion of 18,470 viral connected with predicted hosts at various taxonomic levels

In January 2017, the IMG/VR system [26] -the largest interactive public virus database contained 265,000 metagenomic viral sequences and isolate viruses. This number scaled up to over 760,000 in November 2018 (IMG/VR v.2.0). [27] The IMG/VR systems serve as a starting point for the sequence analysis of viral fragments derived from metagenomic samples.

See also

Related Research Articles

<span class="mw-page-title-main">Bacteriophage</span> Virus that infects and replicates within bacteria

A bacteriophage, also known informally as a phage, is a virus that infects and replicates within bacteria and archaea. The term was derived from "bacteria" and the Greek φαγεῖν, meaning "to devour". Bacteriophages are composed of proteins that encapsulate a DNA or RNA genome, and may have structures that are either simple or elaborate. Their genomes may encode as few as four genes and as many as hundreds of genes. Phages replicate within the bacterium following the injection of their genome into its cytoplasm.

<span class="mw-page-title-main">Virology</span> Study of viruses

Virology is the scientific study of biological viruses. It is a subfield of microbiology that focuses on their detection, structure, classification and evolution, their methods of infection and exploitation of host cells for reproduction, their interaction with host organism physiology and immunity, the diseases they cause, the techniques to isolate and culture them, and their use in research and therapy.

<span class="mw-page-title-main">Metagenomics</span> Study of genes found in the environment

Metagenomics is the study of genetic material recovered directly from environmental or clinical samples by a method called sequencing. The broad field may also be referred to as environmental genomics, ecogenomics, community genomics or microbiomics.

<span class="mw-page-title-main">CRISPR</span> Family of DNA sequence found in prokaryotic organisms

CRISPR is a family of DNA sequences found in the genomes of prokaryotic organisms such as bacteria and archaea. These sequences are derived from DNA fragments of bacteriophages that had previously infected the prokaryote. They are used to detect and destroy DNA from similar bacteriophages during subsequent infections. Hence these sequences play a key role in the antiviral defense system of prokaryotes and provide a form of acquired immunity. CRISPR is found in approximately 50% of sequenced bacterial genomes and nearly 90% of sequenced archaea.

<span class="mw-page-title-main">Integrated Microbial Genomes System</span> Genome browsing and annotation platform

The Integrated Microbial Genomes system is a genome browsing and annotation platform developed by the U.S. Department of Energy (DOE)-Joint Genome Institute. IMG contains all the draft and complete microbial genomes sequenced by the DOE-JGI integrated with other publicly available genomes. IMG provides users a set of tools for comparative analysis of microbial genomes along three dimensions: genes, genomes and functions. Users can select and transfer them in the comparative analysis carts based upon a variety of criteria. IMG also includes a genome annotation pipeline that integrates information from several tools, including KEGG, Pfam, InterPro, and the Gene Ontology, among others. Users can also type or upload their own gene annotations and the IMG system will allow them to generate Genbank or EMBL format files containing these annotations.

<i>Marnaviridae</i> Family of viruses

Marnaviridae is a family of positive-stranded RNA viruses in the order Picornavirales that infect various photosynthetic marine protists. Members of the family have non-enveloped, icosahedral capsids. Replication occurs in the cytoplasm and causes lysis of the host cell. The first species of this family that was isolated is Heterosigma akashiwo RNA virus (HaRNAV) in the genus Marnavirus, which infects the toxic bloom-forming Raphidophyte alga, Heterosigma akashiwo. As of 2021, there are twenty species across seven genera in this family, as well as many other related virus sequences discovered through metagenomic sequencing that are currently unclassified.

<span class="mw-page-title-main">Human Microbiome Project</span> Former research initiative

The Human Microbiome Project (HMP) was a United States National Institutes of Health (NIH) research initiative to improve understanding of the microbiota involved in human health and disease. Launched in 2007, the first phase (HMP1) focused on identifying and characterizing human microbiota. The second phase, known as the Integrative Human Microbiome Project (iHMP) launched in 2014 with the aim of generating resources to characterize the microbiome and elucidating the roles of microbes in health and disease states. The program received $170 million in funding by the NIH Common Fund from 2007 to 2016.

<span class="mw-page-title-main">Virus</span> Infectious agent that replicates in cells

A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea. Viruses are found in almost every ecosystem on Earth and are the most numerous type of biological entity. Since Dmitri Ivanovsky's 1892 article describing a non-bacterial pathogen infecting tobacco plants and the discovery of the tobacco mosaic virus by Martinus Beijerinck in 1898, more than 11,000 of the millions of virus species have been described in detail. The study of viruses is known as virology, a subspeciality of microbiology.

<span class="mw-page-title-main">Forest Rohwer</span> American biologist

Forest Rohwer is an American microbial ecologist and Professor of Biology at San Diego State University. His particular interests include coral reef microbial ecology and viruses as both evolutionary agents and opportunistic pathogens in various environments.

Biological dark matter is an informal term for unclassified or poorly understood genetic material. This genetic material may refer to genetic material produced by unclassified microorganisms. By extension, biological dark matter may also refer to the un-isolated microorganism whose existence can only be inferred from the genetic material that they produce. Some of the genetic material may not fall under the three existing domains of life: Bacteria, Archaea and Eukaryota; thus, it has been suggested that a possible fourth domain of life may yet be discovered, although other explanations are also probable. Alternatively, the genetic material may refer to non-coding DNA and non-coding RNA produced by known organisms.

<span class="mw-page-title-main">Human virome</span> Total collection of viruses in and on the human body

The human virome is the total collection of viruses in and on the human body. Viruses in the human body may infect both human cells and other microbes such as bacteria. Some viruses cause disease, while others may be asymptomatic. Certain viruses are also integrated into the human genome as proviruses or endogenous viral elements.

<span class="mw-page-title-main">Viral metagenomics</span>

Viral metagenomics uses metagenomic technologies to detect viral genomic material from diverse environmental and clinical samples. Viruses are the most abundant biological entity and are extremely diverse; however, only a small fraction of viruses have been sequenced and only an even smaller fraction have been isolated and cultured. Sequencing viruses can be challenging because viruses lack a universally conserved marker gene so gene-based approaches are limited. Metagenomics can be used to study and analyze unculturable viruses and has been an important tool in understanding viral diversity and abundance and in the discovery of novel viruses. For example, metagenomics methods have been used to describe viruses associated with cancerous tumors and in terrestrial ecosystems.

Auxiliary metabolic genes (AMGs) are found in many bacteriophages but originated in bacterial cells. AMGs modulate host cell metabolism during infection so that the phage can replicate more efficiently. For instance, bacteriophages that infect the abundant marine cyanobacteria Synechococcus and Prochlorococcus (cyanophages) carry AMGs that have been acquired from their immediate host as well as more distantly-related bacteria. Cyanophage AMGs support a variety of functions including photosynthesis, carbon metabolism, nucleic acid synthesis and metabolism. AMGs also have broader ecological impacts beyond their host including their influence on biogeochemical cycling.

Nikos Kyrpides is a Greek-American bioscientist who has worked on the origins of life, information processing, bioinformatics, microbiology, metagenomics and microbiome data science. He is a senior staff scientist at the Berkeley National Laboratory, head of the Prokaryote Super Program and leads the Microbiome Data Science program at the US Department of Energy Joint Genome Institute.

<span class="mw-page-title-main">Mya Breitbart</span> American biologist

Mya Breitbart is an American biologist and professor of biological oceanography at the University of South Florida's College of Marine Science. She is best known for her contributions to the field of viral metagenomics. Popular Science recognized her because of her approach of not trying to sequence individual viruses or organisms but to sequence everything in a given ecosystem.

<i>Riboviria</i> Realm of viruses

Riboviria is a realm of viruses that includes all viruses that use a homologous RNA-dependent polymerase for replication. It includes RNA viruses that encode an RNA-dependent RNA polymerase, as well as reverse-transcribing viruses that encode an RNA-dependent DNA polymerase. RNA-dependent RNA polymerase (RdRp), also called RNA replicase, produces RNA from RNA. RNA-dependent DNA polymerase (RdDp), also called reverse transcriptase (RT), produces DNA from RNA. These enzymes are essential for replicating the viral genome and transcribing viral genes into messenger RNA (mRNA) for translation of viral proteins.

<i>Redondoviridae</i> Family of viruses

Redondoviruses are a family of human-associated DNA viruses. Their name derives from the inferred circular structure of the viral genome . Redondoviruses have been identified in DNA sequence based surveys of samples from humans, primarily samples from the oral cavity and upper airway.

<span class="mw-page-title-main">Marine viruses</span> Viruses found in marine environments

Marine viruses are defined by their habitat as viruses that are found in marine environments, that is, in the saltwater of seas or oceans or the brackish water of coastal estuaries. Viruses are small infectious agents that can only replicate inside the living cells of a host organism, because they need the replication machinery of the host to do so. They can infect all types of life forms, from animals and plants to microorganisms, including bacteria and archaea.

Diversity-generating retroelements (DGRs) are a family of retroelements that were first found in Bordetella phage (BPP-1), and since been found in bacteria, Archaea, Archaean viruses, temperate phages, and lytic phages. DGRs benefit their host by mutating particular regions of specific target proteins, for instance, phage tail fiber in BPP-1, lipoprotein in legionella pneumophila, and TvpA in Treponema denticola . An error-prone reverse transcriptase is responsible for generating these hypervariable regions in target proteins. In mutagenic retrohoming, a mutagenized cDNA is reverse transcribed from a template region (TR), and is replaced with a segment similar to the template region called variable region (VR). Accessory variability determinant (Avd) protein is another component of DGRs, and its complex formation with the error-prone RT is of importance to mutagenic rehoming.

Virosphere was coined to refer to all those places in which viruses are found or which are affected by viruses. However, more recently virosphere has also been used to refer to the pool of viruses that occurs in all hosts and all environments, as well as viruses associated with specific types of hosts, type of genome or ecological niche.

References

  1. Anderson NG, Gerin JL, Anderson NL (July 2003). "Global screening for human viral pathogens". Emerging Infectious Diseases. 9 (7): 768–774. doi:10.3201/eid0907.030004. PMC   3023425 . PMID   12890315.
  2. Zárate S, Taboada B, Yocupicio-Monroy M, Arias CF (November 2017). "Human Virome". Archives of Medical Research. 48 (8): 701–716. doi:10.1016/j.arcmed.2018.01.005. PMID   29398104.
  3. McDaniel L, Breitbart M, Mobberley J, Long A, Haynes M, Rohwer F, Paul JH (September 2008). "Metagenomic analysis of lysogeny in Tampa Bay: implications for prophage gene expression". PLOS ONE. 3 (9): e3263. Bibcode:2008PLoSO...3.3263M. doi: 10.1371/journal.pone.0003263 . PMC   2533394 . PMID   18810270.
  4. Wilhelm SW, Suttle CA (1999). "Viruses and Nutrient Cycles in the Sea". BioScience. 49 (10): 781–788. doi: 10.2307/1313569 . ISSN   1525-3244. JSTOR   1313569.
  5. Wegley L, Edwards R, Rodriguez-Brito B, Liu H, Rohwer F (November 2007). "Metagenomic analysis of the microbial community associated with the coral Porites astreoides". Environmental Microbiology. 9 (11): 2707–2719. Bibcode:2007EnvMi...9.2707W. doi:10.1111/j.1462-2920.2007.01383.x. PMID   17922755.
  6. Barr JJ, Auro R, Furlan M, Whiteson KL, Erb ML, Pogliano J, et al. (June 2013). "Bacteriophage adhering to mucus provide a non-host-derived immunity". Proceedings of the National Academy of Sciences of the United States of America. 110 (26): 10771–10776. Bibcode:2013PNAS..11010771B. doi: 10.1073/pnas.1305923110 . PMC   3696810 . PMID   23690590.
  7. Sharon I, Battchikova N, Aro EM, Giglione C, Meinnel T, Glaser F, et al. (July 2011). "Comparative metagenomics of microbial traits within oceanic viral communities". The ISME Journal. 5 (7): 1178–1190. Bibcode:2011ISMEJ...5.1178S. doi:10.1038/ismej.2011.2. PMC   3146289 . PMID   21307954.
  8. Pyöriä L, Pratas D, Toppinen M, Hedman K, Sajantila A, Perdomo MF (2023). "Unmasking the tissue-resident eukaryotic DNA virome in humans". Nucleic Acids Research. 51 (7): 3223–3239. doi:10.1093/nar/gkad199. PMC   10123123 . PMID   36951096.
  9. 1 2 Breitbart M, Salamon P, Andresen B, Mahaffy JM, Segall AM, Mead D, et al. (October 2002). "Genomic analysis of uncultured marine viral communities". Proceedings of the National Academy of Sciences of the United States of America. 99 (22): 14250–14255. Bibcode:2002PNAS...9914250B. doi: 10.1073/pnas.202488399 . PMC   137870 . PMID   12384570.
  10. Angly FE, Felts B, Breitbart M, Salamon P, Edwards RA, Carlson C, et al. (November 2006). "The marine viromes of four oceanic regions". PLOS Biology. 4 (11): e368. doi: 10.1371/journal.pbio.0040368 . PMC   1634881 . PMID   17090214.
  11. Breitbart M, Felts B, Kelley S, Mahaffy JM, Nulton J, Salamon P, Rohwer F (March 2004). "Diversity and population structure of a near-shore marine-sediment viral community". Proceedings. Biological Sciences. 271 (1539): 565–574. doi:10.1098/rspb.2003.2628. PMC   1691639 . PMID   15156913.
  12. Breitbart M, Hewson I, Felts B, Mahaffy JM, Nulton J, Salamon P, Rohwer F (October 2003). "Metagenomic analyses of an uncultured viral community from human feces". Journal of Bacteriology. 185 (20): 6220–6223. doi:10.1128/jb.185.20.6220-6223.2003. PMC   225035 . PMID   14526037.
  13. Breitbart M, Haynes M, Kelley S, Angly F, Edwards RA, Felts B, et al. (June 2008). "Viral diversity and dynamics in an infant gut". Research in Microbiology. 159 (5): 367–373. doi: 10.1016/j.resmic.2008.04.006 . PMID   18541415.
  14. Fierer N, Breitbart M, Nulton J, Salamon P, Lozupone C, Jones R, et al. (November 2007). "Metagenomic and small-subunit rRNA analyses reveal the genetic diversity of bacteria, archaea, fungi, and viruses in soil". Applied and Environmental Microbiology. 73 (21): 7059–7066. Bibcode:2007ApEnM..73.7059F. doi:10.1128/aem.00358-07. PMC   2074941 . PMID   17827313.
  15. Breitbart M, Rohwer F (November 2005). "Method for discovering novel DNA viruses in blood using viral particle selection and shotgun sequencing". BioTechniques. 39 (5): 729–736. doi: 10.2144/000112019 . PMID   16312220.
  16. Zhang T, Breitbart M, Lee WH, Run JQ, Wei CL, Soh SW, et al. (January 2006). "RNA viral community in human feces: prevalence of plant pathogenic viruses". PLOS Biology. 4 (1): e3. doi: 10.1371/journal.pbio.0040003 . PMC   1310650 . PMID   16336043.
  17. Edwards RA, Rohwer F (June 2005). "Viral metagenomics". Nature Reviews. Microbiology. 3 (6): 504–510. doi:10.1038/nrmicro1163. PMID   15886693. S2CID   8059643.
  18. Rohwer F (April 2003). "Global phage diversity". Cell. 113 (2): 141. doi: 10.1016/s0092-8674(03)00276-9 . PMID   12705861.
  19. Garmaeva S, Sinha T, Kurilshikov A, Fu J, Wijmenga C, Zhernakova A (October 2019). "Studying the gut virome in the metagenomic era: challenges and perspectives". BMC Biology. 17 (1): 84. doi: 10.1186/s12915-019-0704-y . PMC   6819614 . PMID   31660953.
  20. Shkoporov AN, Clooney AG, Sutton TD, Ryan FJ, Daly KM, Nolan JA, et al. (October 2019). "The Human Gut Virome Is Highly Diverse, Stable, and Individual Specific". Cell Host & Microbe. 26 (4): 527–541.e5. doi: 10.1016/j.chom.2019.09.009 . PMID   31600503. S2CID   204242937.
  21. Clooney AG, Sutton TD, Shkoporov AN, Holohan RK, Daly KM, O'Regan O, et al. (December 2019). "Whole-Virome Analysis Sheds Light on Viral Dark Matter in Inflammatory Bowel Disease". Cell Host & Microbe. 26 (6): 764–778.e5. doi: 10.1016/j.chom.2019.10.009 . PMID   31757768. S2CID   208234961.
  22. Thurber RV, Haynes M, Breitbart M, Wegley L, Rohwer F (2009). "Laboratory procedures to generate viral metagenomes". Nature Protocols. 4 (4): 470–483. doi:10.1038/nprot.2009.10. PMID   19300441. S2CID   205464352.
  23. Paez-Espino D, Pavlopoulos GA, Ivanova NN, Kyrpides NC (August 2017). "Nontargeted virus sequence discovery pipeline and virus clustering for metagenomic data". Nature Protocols. 12 (8): 1673–1682. doi:10.1038/nprot.2017.063. PMID   28749930. S2CID   2127494.
  24. Tang L (July 2019). "Pole-to-pole ocean viromes". Research highlights. Nature Methods (Paper). 16 (7): 575. doi: 10.1038/s41592-019-0480-1 . PMID   31249411.  via Springer Nature (subscription required)
  25. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Paez-Espino D, Eloe-Fadrosh EA, Pavlopoulos GA, Thomas AD, Huntemann M, Mikhailova N, et al. (August 2016). "Uncovering Earth's virome". Nature. 536 (7617): 425–430. Bibcode:2016Natur.536..425P. doi:10.1038/nature19094. PMID   27533034. S2CID   4466854.
  26. Paez-Espino D, Chen IA, Palaniappan K, Ratner A, Chu K, Szeto E, et al. (January 2017). "IMG/VR: a database of cultured and uncultured DNA Viruses and retroviruses". Nucleic Acids Research. 45 (D1): D457–D465. doi:10.1093/nar/gkw1030. PMC   5210529 . PMID   27799466.
  27. Paez-Espino D, Roux S, Chen IA, Palaniappan K, Ratner A, Chu K, et al. (January 2019). "IMG/VR v.2.0: an integrated data management and analysis system for cultivated and environmental viral genomes". Nucleic Acids Research. 47 (D1): D678–D686. doi:10.1093/nar/gky1127. PMC   6323928 . PMID   30407573.