Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Diversity and evolution of the animal virome

Nature Reviews Microbiology volume 20, pages 321–334 (2022)Cite this article

Subjects

Abstract

The COVID-19 pandemic has given the study of virus evolution and ecology new relevance. Although viruses were first identified more than a century ago, we likely know less about their diversity than that of any other biological entity. Most documented animal viruses have been sampled from just two phyla — the Chordata and the Arthropoda — with a strong bias towards viruses that infect humans or animals of economic and social importance, often in association with strong disease phenotypes. Fortunately, the recent development of unbiased metagenomic next-generation sequencing is providing a richer view of the animal virome and shedding new light on virus evolution. In this Review, we explore our changing understanding of the diversity, composition and evolution of the animal virome. We outline the factors that determine the phylogenetic diversity and genomic structure of animal viruses on evolutionary timescales and show how this impacts assessment of the risk of disease emergence in the short term. We also describe the ongoing challenges in metagenomic analysis and outline key themes for future research. A central question is how major events in the evolutionary history of animals, such as the origin of the vertebrates and periodic mass extinction events, have shaped the diversity and evolution of the viruses they carry.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: Phylogenetic diversity of animal viruses.
Fig. 2: Virome sequencing by animal phylum.
Fig. 3: Recent phylogenetic and genomic expansion of the coronaviruses.
Fig. 4: The complexity of host associations in virus evolution.
Fig. 5: The evolutionary flexibility of RNA virus genomes.

Similar content being viewed by others

References

  1. Wasik, B. R. & Turner, P. E. On the biological success of viruses. Annu. Rev. Microbiol. 67, 519–541 (2013).

    Article  CAS  PubMed  Google Scholar 

  2. Holmes, E. C. The Evolution and Emergence of RNA Viruses (Oxford University Press, 2009).

  3. Loeffler, F. A. J. & Frosch, P. Berichte der Kommission zur Erforschung der Maul- und Klauenseuche bei dem Institut für Infektionskrankheiten in Berlin (G. Fischer, 1898).

  4. Kumar, A., Murthy, S. & Kapoor, A. Evolution of selective-sequencing approaches for virus discovery and virome analysis. Virus Res. 239, 172–179 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Shi, M. et al. Redefining the invertebrate RNA virosphere. Nature 540, 539–543 (2016).

    Article  CAS  PubMed  Google Scholar 

  6. Shi, M. et al. Divergent viruses discovered in arthropods and vertebrates revise the evolutionary history of the Flaviviridae and related viruses. J. Virol. 90, 659–669 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  7. Zhang, Y. Z., Shi, M. & Holmes, E. C. Using metagenomics to characterize an expanding virosphere. Cell 172, 1168–1172 (2018).

    Article  CAS  PubMed  Google Scholar 

  8. Ambrose, H. E. & Clewley, J. P. Virus discovery by sequence-independent genome amplification. Rev. Med. Virol. 16, 365–383 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Shi, M. et al. The evolutionary history of vertebrate RNA viruses. Nature 556, 197–202 (2018). Major study of the phylogenetic diversity of RNA viruses carried by diverse vertebrates, showing that many of the virus families associated with mammals have a deep ancestry with evolutionary roots in fish.

    Article  CAS  PubMed  Google Scholar 

  10. Buchfink, B., Reuter, K. & Drost, H. G. Sensitive protein alignments at tree-of-life scale using diamond. Nat. Methods 18, 366–368 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Geoghegan, J. L. & Holmes, E. C. Predicting virus emergence amid evolutionary noise. Open Biol. 7, 170189 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Fernández, R. & Gabaldón, T. Gene gain and loss across the metazoan tree of life. Nat. Ecol. Evol. 4, 524–533 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Laumer, C. E. et al. Revisiting metazoan phylogeny with genomic sampling of all phyla. Proc. Biol. Sci. 286, 20190831 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Paraskevopoulou, S. et al. Viromics of extant insect orders unveil the evolution of the flavi-like superfamily. Virus Evol. 7, veab030 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  15. Murphy, F. A. Historical perspective: what constitutes discovery (of a new virus)? Adv. Virus Res. 95, 197–220 (2016).

    Article  CAS  PubMed  Google Scholar 

  16. Greninger, A. L. A decade of RNA virus metagenomics is (not) enough. Virus Res. 244, 218–229 (2018).

    Article  CAS  PubMed  Google Scholar 

  17. Li, C. X. et al. Unprecedented genomic diversity of RNA viruses in arthropods reveals the ancestry of negative-sense RNA viruses. eLife 4, e05378 (2015). First article to show that invertebrates — in this case arthropods — harbour an enormous diversity of RNA viruses, often at high abundance. Provides the first description of the chuviruses, which are characterized by diverse genome structures.

    Article  PubMed Central  CAS  Google Scholar 

  18. Donaldson, E. F. et al. Metagenomic analysis of the viromes of three North American bat species: viral diversity among different bat species that share a common habitat. J. Virol. 84, 13004–13018 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Li, L. et al. The fecal viral flora of California sea lions. J. Virol. 85, 9909–9917 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ge, X. et al. Metagenomic analysis of viruses from bat fecal samples reveals many novel viruses in insectivorous bats in China. J. Virol. 86, 4620–4630 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Walker, P. J. et al. Changes to virus taxonomy and to the International Code of Virus Classification and Nomenclature ratified by the International Committee on Taxonomy of Viruses (2021). Arch. Virol. https://doi.org/10.1007/s00705-021-05156-1 (2021).

    Article  PubMed  Google Scholar 

  22. Lauber, C. et al. Deciphering the origin and evolution of hepatitis B viruses by means of a family of non-enveloped fish viruses. Cell Host Microbe 22, 387–399.e386 (2017). Major study of the phylogenetic diversity of HBV-like viruses in fish, including the discovery of a group of related viruses — the nackednaviruses — that lack the envelope protein.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Geoghegan, J. L. et al. Hidden diversity and evolution of viruses in market fish. Virus Evol. 4, vey031 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Zeigler Allen, L. et al. The Baltic Sea virome: diversity and transcriptional activity of DNA and RNA viruses. mSystems 2, e00125–16 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  25. Parry, R., Wille, M., Turnbull, O. M. H., Geoghegan, J. L. & Holmes, E. C. Divergent influenza-like viruses of amphibians and fish support an ancient evolutionary association. Viruses 12, 1042 (2020).

    Article  CAS  PubMed Central  Google Scholar 

  26. Geoghegan, J. L. et al. Virome composition in marine fish revealed by meta-transcriptomics. Virus Evol. 7, veab005 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Costa, V. A. et al. Metagenomic sequencing reveals a lack of virus exchange between native and invasive freshwater fish across the Murray–Darling Basin, Australia. Virus Evol. 7, veab034 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  28. Miller, A. K. et al. Slippery when wet: cross-species transmission of divergent coronaviruses in bony and jawless fish and the evolutionary history of the Coronaviridae. Virus Evol. 7, veab050 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  29. López-Bueno, A. et al. Concurrence of iridovirus, polyomavirus, and a unique member of a new group of fish papillomaviruses in lymphocystis disease-affected gilthead sea bream. J. Virol. 90, 8768–8779 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Wu, F. et al. A new coronavirus associated with human respiratory disease in China. Nature 579, 265–269 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Lu, R. et al. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet 395, 565–574 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Wang, W. et al. Extensive genetic diversity and host range of rodent-borne coronaviruses. Virus Evol. 6, veaa078 (2021).

    Article  Google Scholar 

  33. Latinne, A. et al. Origin and cross-species transmission of bat coronaviruses in China. Nat. Commun. 11, 4235 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Temmam, S. et al. Coronaviruses with a SARS-CoV-2-like receptor-binding domain allowing ACE2-mediated entry into human cells isolated from bats of Indochinese peninsula. Preprint at Research Square https://doi.org/10.21203/rs.3.rs-871965/v1 (2021).

    Article  Google Scholar 

  35. van Aart, A. E. et al. SARS-CoV-2 infection in cats and dogs in infected mink farms. Transbound. Emerg. Dis. https://doi.org/10.1111/tbed.14173 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  36. Oude Munnink, B. B. et al. Transmission of SARS-CoV-2 on mink farms between humans and mink and back to humans. Science 371, 172–177 (2021). Demonstration of the broad host range of SARS-CoV-2, reflected in a major outbreak in farmed mink. That the virus was able to spread back to humans shows that some animal species may become SARS-CoV-2 reservoirs.

    Article  CAS  PubMed  Google Scholar 

  37. Chandler, J. C. et al. SARS-CoV-2 exposure in wild white-tailed deer (Odocoileus virginianus). Preprint at bioRxiv https://doi.org/10.1101/2021.07.29.454326 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  38. Lam, T. T.-Y. et al. Identifying SARS-CoV-2 related coronaviruses in Malayan pangolins. Nature 583, 282–285 (2020).

    Article  CAS  PubMed  Google Scholar 

  39. Zhou, H. et al. Identification of novel bat coronaviruses sheds light on the evolutionary origins of SARS-CoV-2 and related viruses. Cell 184, 4380–4391 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Corman, V. M., Muth, D., Niemeyer, D. & Drosten, C. Hosts and sources of endemic human coronaviruses. Adv. Virus Res. 100, 163–188 (2018). Important review of the human coronaviruses highlighting their diversity, evolutionary history and zoonotic origins.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Edgar, R. C. et al. Petabase-scale sequence alignment catalyses viral discovery. Preprint at bioRxiv https://doi.org/10.1101/2020.08.07.241729 (2020).

    Article  Google Scholar 

  42. Salehi-Ashtiani, K., Lupták, A., Litovchick, A. & Szostak, J. W. A genomewide search for ribozymes reveals an HDV-like sequence in the human CPEB3 gene. Science 313, 1788–1792 (2006).

    Article  CAS  PubMed  Google Scholar 

  43. Chang, W.-S. et al. Novel hepatitis D-like agents in vertebrates and invertebrates. Virus Evol. 5, vez021 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  44. Hetzel, U. et al. Identification of a novel deltavirus in boa constrictors. mBio 10, e00014-19 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Iwamoto, M. et al. Identification of novel avian and mammalian deltaviruses provides new insights into deltavirus evolution. Virus Evol. 7, veab003 (2021). Overview of the evolution of deltaviruses (that is, HDV-like viruses) in birds and mammals. Reveals the ancient history and diversity of these viruses and shows that they are not exclusively associated with humans or HBV.

    Article  PubMed  PubMed Central  Google Scholar 

  46. Paraskevopoulou, S. et al. Mammalian deltavirus without hepadnavirus coinfection in the neotropical rodent Proechimys semispinosus. Proc. Natl Acad. Sci. USA 117, 17977–17983 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Taubenberger, J. K. & Kash, J. C. Influenza virus evolution, host adaptation, and pandemic formation. Cell Host Microbe 7, 440–451 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Joseph, U., Su, Y. C., Vijaykrishna, D. & Smith, G. J. The ecology and adaptive evolution of influenza A interspecies transmission. Influenza Other Respir. Viruses 11, 74–84 (2017).

    Article  PubMed  Google Scholar 

  49. Wu, H. et al. Abundant and diverse RNA viruses in insects revealed by RNA-Seq analysis: ecological and evolutionary implications. mSystems 5, e00039-20 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Van Eynde, B. et al. Exploration of the virome of the European brown shrimp (Crangon crangon). J. Gen. Virol. 101, 651–666 (2020).

    Article  PubMed  CAS  Google Scholar 

  51. Laffy, P. W. et al. Reef invertebrate viromics: diversity, host specificity and functional capacity. Environ. Microbiol. 20, 2125–2141 (2018).

    Article  PubMed  Google Scholar 

  52. Tokarz, R. et al. Virome analysis of Amblyomma americanum, Dermacentor variabilis, and Ixodes scapularis ticks reveals novel highly divergent vertebrate and invertebrate viruses. J. Virol. 88, 11480–11492 (2014).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Käfer, S. et al. Re-assessing the diversity of negative strand RNA viruses in insects. PLoS Pathog. 15, e1008224 (2019).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Ramírez, A. L. et al. Metagenomic analysis of the virome of mosquito excreta. mSphere 5, e00587-20 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  55. Brinkmann, A. et al. A metagenomic survey identifies Tamdy orthonairovirus as well as divergent phlebo-, rhabdo-, chu- and flavi-like viruses in Anatolia, Turkey. Ticks Tick. Borne Dis. 9, 1173–1183 (2018).

    Article  PubMed  Google Scholar 

  56. Gudenkauf, B. M. & Hewson, I. Comparative metagenomics of viral assemblages inhabiting four phyla of marine invertebrates. Front. Mar. Sci. 3, 23 (2016).

    Article  Google Scholar 

  57. Medd, N. C. et al. The virome of Drosophila suzukii, an invasive pest of soft fruit. Virus Evol. 4, vey009 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  58. Webster, C. L. et al. The discovery, distribution, and evolution of viruses associated with Drosophila melanogaster. PLoS Biol. 13, e1002210 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Hameed, M. et al. A metagenomic analysis of mosquito virome collected from different animal farms at Yunnan–Myanmar border of China. Front. Microbiol. 11, 591478 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  60. Sadeghi, M. et al. Virome of >12 thousand Culex mosquitoes from throughout California. Virology 523, 74–88 (2018). Major metagenomic study of virome diversity in mosquitoes showing the power of this technology for high-throughput virus screening at a single location.

    Article  CAS  PubMed  Google Scholar 

  61. He, X. et al. Metagenomic sequencing reveals viral abundance and diversity in mosquitoes from the Shaanxi-Gansu-Ningxia region, China. PLoS Negl. Trop. Dis. 15, e0009381 (2021).

    Article  PubMed  PubMed Central  Google Scholar 

  62. Marklewitz, M., Zirkel, F., Kurth, A., Drosten, C. & Junglen, S. Evolutionary and phenotypic analysis of live virus isolates suggests arthropod origin of a pathogenic RNA virus family. Proc. Natl Acad. Sci. USA 112, 7536–7541 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Schmidlin, K. et al. A novel lineage of polyomaviruses identified in bark scorpions. Virology 563, 58–63 (2021).

    Article  CAS  PubMed  Google Scholar 

  64. Qin, X. C. et al. A tick-borne segmented RNA virus contains genome segments derived from unsegmented viral ancestors. Proc. Natl Acad. Sci. USA 111, 6744–6749 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Ladner, J. T. et al. A multicomponent animal virus isolated from mosquitoes. Cell Host Microbe 20, 357–367 (2016). First description of a multicomponent virus in an animal. Highlights the complexity of genome evolution in RNA viruses, in this case in the flavi-like viruses.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Argenta, F. F. et al. Identification of reptarenaviruses, hartmaniviruses, and a novel chuvirus in captive native Brazilian boa constrictors with boid inclusion body disease. J. Virol. 94, e00001-20 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  67. Sharp, P. M. & Hahn, B. H. Origins of HIV and the AIDS pandemic. Cold Spring Harb. Perspect. Med. 1, a006841 (2011).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Pybus, O. G., Rambaut, A., Holmes, E. C. & Harvey, P. H. New inferences from tree shape: numbers of missing taxa and population growth rates. Syst. Biol. 51, 881–888 (2002).

    Article  CAS  PubMed  Google Scholar 

  69. Kapusinszky, B. et al. Local virus extinctions following a host population bottleneck. J. Virol. 89, 8152–8161 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. McKee, C. D., Bai, Y., Webb, C. T. & Kosoy, M. Y. Bats are key hosts in the radiation of mammal-associated Bartonella bacteria. Infect. Genet. Evol. 89, 104719 (2021).

    Article  CAS  PubMed  Google Scholar 

  71. dos Reis, M. et al. Uncertainty in the timing of origin of animals and the limits of precision in molecular timescales. Curr. Biol. 25, 2939–2950 (2015).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Flajnik, M. F. & Kasahara, M. Origin and evolution of the adaptive immune system: genetic events and selective pressures. Nat. Rev. Genet. 11, 47–59 (2010).

    Article  CAS  PubMed  Google Scholar 

  73. Wang, L.-F., Walker, P. J. & Poon, L. L. M. Mass extinctions, biodiversity and mitochondrial function: are bats ‘special’ as reservoirs for emerging viruses? Curr. Opin. Virol. 1, 649–657 (2011). One of the first articles to propose that bats are uniquely important hosts for emerging viruses and that host mass extinction events might play a key role in shaping the phylogenetic diversity of viruses.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Stanley, S. M. Estimates of the magnitudes of major marine mass extinctions in earth history. Proc. Natl Acad. Sci. USA 113, E6325–E6334 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Raup, D. M. & Sepkoski, J. J. Mass extinctions in the marine fossil record. Science 215, 1501–1503 (1982).

    Article  CAS  PubMed  Google Scholar 

  76. Lynch, M. & Conery, J. S. The origins of genome complexity. Science 302, 1401–1404 (2003).

    Article  CAS  PubMed  Google Scholar 

  77. Carlson, C. J., Zipfel, C. M., Garnier, R. & Bansal, S. Global estimates of mammalian viral diversity accounting for host sharing. Nat. Ecol. Evol. 3, 1070–1075 (2019).

    Article  PubMed  Google Scholar 

  78. Geoghegan, J. L., Duchêne, S. & Holmes, E. C. Comparative analysis estimates the relative frequencies of co-divergence and cross-species transmission within viral families. PLoS Pathog. 13, e1006215 (2017).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  79. Racaniello, V. Moving beyond metagenomics to find the next pandemic virus. Proc. Natl Acad. Sci. USA 113, 2812–2814 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Morse, S. S. et al. Prediction and prevention of the next pandemic zoonosis. Lancet 380, 1956–1965 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  81. Smith, I. & Wang, L. F. Bats and their virome: an important source of emerging viruses capable of infecting humans. Curr. Opin. Virol. 3, 84–91 (2013).

    Article  PubMed  Google Scholar 

  82. Olival, K. J. et al. Host and viral traits predict zoonotic spillover from mammals. Nature 546, 646–650 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Wasik, B. R. et al. Onward transmission of viruses: how do viruses emerge to cause epidemics after spillover? Philos. Trans. R. Soc. Lond. B Biol. Sci. 374, 20190017 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Düx, A. et al. Measles virus and rinderpest virus divergence dated to the sixth century BCE. Science 368, 1367–1370 (2020).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Tabachnick, W. J. Climate change and the arboviruses: lessons from the evolution of the dengue and yellow fever viruses. Annu. Rev. Virol. 3, 125–145 (2016).

    Article  CAS  PubMed  Google Scholar 

  86. Fritzell, C. et al. Current challenges and implications for dengue, chikungunya and Zika seroprevalence studies worldwide: a scoping review. PLoS Negl. Trop. Dis. 12, e0006533 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  87. Campbell-Lendrum, D., Manga, L., Bagayoko, M. & Sommerfeld, J. Climate change and vector-borne diseases: what are the implications for public health research and policy? Philos. Trans. R. Soc. Lond. B. Biol. Sci. 370, 20130552 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  88. Jacob, S. T. et al. Ebola virus disease. Nat. Rev. Dis. Prim. 6, 13 (2020).

    Article  PubMed  Google Scholar 

  89. Gould, E. A. & Higgs, S. Impact of climate change and other factors on emerging arbovirus diseases. Trans. R. Soc. Trop. Med. Hyg. 103, 109–121 (2009).

    Article  CAS  PubMed  Google Scholar 

  90. Marcondes, M. & Day, M. J. Current status and management of canine leishmaniasis in Latin America. Res. Vet. Sci. 123, 261–272 (2019).

    Article  PubMed  Google Scholar 

  91. Brock, P. M. et al. Predictive analysis across spatial scales links zoonotic malaria to deforestation. Proc. Biol. Sci. 286, 20182351 (2019).

    PubMed  PubMed Central  Google Scholar 

  92. Ayala, A. J., Yabsley, M. J. & Hernandez, S. M. A review of pathogen transmission at the backyard chicken–wild bird interface. Front. Vet. Sci. 7, 662 (2020).

    Article  Google Scholar 

  93. Munoz, O. et al. Genetic adaptation of influenza A viruses in domestic animals and their potential role in interspecies transmission: a literature review. Ecohealth 13, 171–198 (2016).

    Article  PubMed  Google Scholar 

  94. Peiris, J. S., de Jong, M. D. & Guan, Y. Avian influenza virus (H5N1): a threat to human health. Clin. Microbiol. Rev. 20, 243–267 (2007). Review of the ecology and evolution of H5N1 avian influenza virus, particularly how it emerges in humans from its avian reservoir populations and its associated pandemic risk.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Schelling, E., Thur, B., Griot, C. & Audige, L. Epidemiological study of Newcastle disease in backyard poultry and wild bird populations in Switzerland. Avian Pathol. 28, 263–272 (1999).

    Article  CAS  PubMed  Google Scholar 

  96. Boros, Á. et al. A diarrheic chicken simultaneously co-infected with multiple picornaviruses: complete genome analysis of avian picornaviruses representing up to six genera. Virology 489, 63–74 (2016).

    Article  CAS  PubMed  Google Scholar 

  97. Lang, A. S. et al. Assessing the role of seabirds in the ecology of influenza A viruses. Avian Dis. 60, 378–386 (2016).

    Article  PubMed  Google Scholar 

  98. Lickfett, T. M., Clark, E., Gehring, T. M. & Alm, E. W. Detection of influenza A viruses at migratory bird stopover sites in Michigan, USA. Infect. Ecol. Epidemiol. 8, 1474709 (2018).

    PubMed  PubMed Central  Google Scholar 

  99. Rezza, G. Dengue and chikungunya: long-distance spread and outbreaks in naïve areas. Pathog. Glob. Health 108, 349–355 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  100. Fritzsche McKay, A. & Hoye, B. J. Are migratory animals superspreaders of infection? Integr. Comp. Biol. 56, 260–267 (2016).

    Article  PubMed  Google Scholar 

  101. Jeong, S. et al. Introduction of avian influenza A(H6N5) virus into Asia from North America by wild birds. Emerg. Infect. Dis. 25, 2138–2140 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  102. Pettersson, J. H. O. et al. Circumpolar diversification of the Ixodes uriae tick virome. PLoS Pathog. 16, e1008759 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Albery, G. F., Eskew, E. A., Ross, N. & Olival, K. J. Predicting the global mammalian viral sharing network using phylogeography. Nat. Commun. 11, 2260 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Dill, J. A. et al. Distinct viral lineages from fish and amphibians reveal the complex evolutionary history of hepadnaviruses. J. Virol. 90, 7920–7933 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Mollentze, N. & Streicker, D. G. Viral zoonotic risk is homogenous among taxonomic orders of mammalian and avian reservoir hosts. Proc. Natl Acad. Sci. USA 117, 9423–9430 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Mollentze, N., Babayan, S. A. & Streicker, D. G. Identifying and prioritizing potential human-infecting viruses from their genome sequences. PLoS Biol. 19, e3001390 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Wille, M., Geoghegan, J. L. & Holmes, E. C. How accurately can we assess zoonotic risk? PLoS Biol. 19, e3001135 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Kohl, C. et al. The virome of German bats: comparing virus discovery approaches. Sci. Rep. 11, 7430 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Li, L. et al. Bat guano virome: predominance of dietary viruses from insects and plants plus novel mammalian viruses. J. Virol. 84, 6955–6965 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Kemenesi, G. et al. Molecular survey of RNA viruses in Hungarian bats: discovering novel astroviruses, coronaviruses, and caliciviruses. Vector Borne Zoonotic Dis. 14, 846–855 (2014).

    Article  PubMed  Google Scholar 

  111. Letko, M., Seifert, S. N., Olival, K. J., Plowright, R. K. & Munster, V. J. Bat-borne virus diversity, spillover and emergence. Nat. Rev. Microbiol. 18, 461–471 (2020). Extensive review of the relevant biology of bats and the viruses they carry, particularly in the context of SARS-CoV-2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Irving, A. T., Ahn, M., Goh, G., Anderson, D. E. & Wang, L.-F. Lessons from the host defences of bats, a unique viral reservoir. Nature 589, 363–370 (2021). Timely review outlining the reasons why bats might be uniquely important virus reservoirs and what this might mean for understanding future emergence events.

    Article  CAS  PubMed  Google Scholar 

  113. Banerjee, A. et al. Novel insights into immune systems of bats. Front. Immunol. 11, 26 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Holmes, E. C., Rambaut, A. & Andersen, K. G. Pandemics: spend on surveillance, not prediction. Nature 558, 180–182 (2018).

    Article  CAS  PubMed  Google Scholar 

  115. Sanjuán, R. & Domingo-Calap, P. Mechanisms of viral mutation. Cell Mol. Life Sci. 73, 4433–4448 (2016).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  116. Plowright, R. K. et al. Pathways to zoonotic spillover. Nat. Rev. Microbiol. 15, 502–510 (2017). Benchmark review of the ecological processes by which viruses can spill over and emerge in new hosts, identifying this as a key process in virus evolution.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Holmes, E. C. et al. The origins of SARS-CoV-2: a critical review. Cell 184, 4848–4856 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Johnson, B. A. et al. Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis. Nature 591, 293–299 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Wrobel, A. G. SARS-CoV-2 and bat RaTG13 spike glycoprotein structures inform on virus evolution and furin-cleavage effects. Nat. Struct. Mol. Biol. 27, 763–767 (2020). Detailed structural virology study that demonstrates that even closely related human and animal coronaviruses can differ profoundly in receptor-binding ability.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Wilson, M. R. et al. Chronic meningitis investigated via metagenomic next-generation sequencing. JAMA Neurol. 75, 947–955 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  121. Wilson, M. R. et al. Clinical metagenomic sequencing for diagnosis of meningitis and encephalitis. N. Engl. J. Med. 380, 2327–2340 (2019). Key article showing the importance of mNGS in a clinical diagnostic setting, in this case for the identification of the microbial pathogens associated with meningitis and encephalitis.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Xu, G. J. et al. Comprehensive serological profiling of human populations using a synthetic human virome. Science 348, aaa0698 (2015). Presents VirScan — a method for the high-throughput screening of viruses by identifying antiviral antibodies in human sera. Although originally designed to screen the human virome, the method could be adapted to detect zoonotic viruses.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Field, H. E., Mackenzie, J. S. & Daszak, P. Henipaviruses: emerging paramyxoviruses associated with fruit bats. Curr. Top. Microbiol. Immunol. 315, 133–159 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. Harvey, E. et al. Extensive diversity of RNA viruses in Australian ticks. J. Virol. 93, e01358-18 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  125. Wille, M. et al. Sustained RNA virome diversity in Antarctic penguins and their ticks. ISME J. 14, 1768–1782 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  126. Di Giallonardo, F., Schlub, T. E., Shi, M. & Holmes, E. C. Dinucleotide composition in RNA viruses is shaped more by virus family than host species. J. Virol. 91, e02381-16 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  127. Krishnamurthy, S. R. & Wang, D. Origins and challenges of viral dark matter. Virus Res. 239, 136–142 (2017).

    Article  CAS  PubMed  Google Scholar 

  128. Bamford, D. H., Grimes, J. M. & Stuart, D. I. What does structure tell us about virus evolution? Curr. Opin. Struct. Biol. 15, 655–663 (2005). Demonstrates how patterns of evolutionary relatedness are preserved in the structure of viral capsid proteins. Lays the foundation for how protein structural information can be used to infer phylogenetic relationships.

    Article  CAS  PubMed  Google Scholar 

  129. Illergård, K., Ardell, D. H. & Elofsson, A. Structure is three to ten times more conserved than sequence — a study of structural response in protein cores. Proteins 77, 499–508 (2009).

    Article  PubMed  CAS  Google Scholar 

  130. Harrison, S. C. Viral membrane fusion. Nat. Struct. Mol. Biol. 15, 690–698 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Fédry, J. et al. The ancient gamete fusogen HAP2 is a eukaryotic class II fusion protein. Cell 168, 904–915 (2017). Demonstration of how protein structure can reveal ancient evolutionary homologies, in this case between an algal gamete fusogen and a class II viral membrane fusion protein.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  132. Henderson, R. Overview and future of single particle electron cryomicroscopy. Arch. Biochem. Biophys. 581, 19–24 (2015).

    Article  CAS  PubMed  Google Scholar 

  133. Eddy, S. R. Accelerated profile HMM searches. PLoS Comp. Biol. 7, e1002195 (2011).

    Article  CAS  Google Scholar 

  134. Krupovic, M., Cvirkaite-Krupovic, V., Iranzo, J., Prangishvili, D. & Koonin, E. V. Viruses of Archaea: structural, functional, environmental and evolutionary genomics. Virus Res. 244, 181–193 (2018).

    Article  CAS  PubMed  Google Scholar 

  135. Holmes, E. C. & Duchêne, S. Can sequence phylogenies safely infer the origin of the global virome? mBio 10, e00289-19 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  136. Chang, G. S. et al. Phylogenetic profiles reveal evolutionary relationships within the ‘twilight zone’ of sequence similarity. Proc. Natl Acad. Sci. USA 105, 13474–13479 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Nguyen, L.-T., Schmidt, H. A., von Haeseler, A. & Minh, B. Q. IQ-TREE: A fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol. Biol. Evol. 32, 268–274 (2015).

    Article  CAS  PubMed  Google Scholar 

  138. Wooley, J. C., Godzik, A. & Friedberg, I. A primer on metagenomics. PLoS Comp. Biol. 6, e10006677 (2010).

    Article  CAS  Google Scholar 

  139. O’Neil, D., Glowatz, H. & Schlumpberger, M. Ribosomal RNA depletion for efficient use of RNA-seq capacity. Curr. Protoc. Mol. Biol. https://doi.org/10.1002/0471142727.mb0419s103 (2013).

    Article  PubMed  Google Scholar 

  140. Briese, T. et al. Virome capture sequencing enables sensitive viral diagnosis and comprehensive virome analysis. mBio 6, e01491-15 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  141. Chong, R. et al. Fecal viral diversity of captive and wild Tasmanian devils characterized using virion-enriched metagenomics and metatranscriptomics. J. Virol. 93, e00205-19 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Sydney Institute for Infectious Diseases, University of Sydney, Sydney, NSW, Australia

    Erin Harvey & Edward C. Holmes

  2. School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia

    Erin Harvey & Edward C. Holmes

  3. School of Medical Sciences, University of Sydney, Sydney, NSW, Australia

    Erin Harvey & Edward C. Holmes

Authors
  1. Erin Harvey
    View author publications

    Search author on:PubMed Google Scholar

  2. Edward C. Holmes
    View author publications

    Search author on:PubMed Google Scholar

Contributions

E.H. researched data for the article. Both authors contributed substantially to discussion of the content, wrote the article, and edited and reviewed the manuscript before submission.

Corresponding author

Correspondence to Edward C. Holmes.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Peer review information

Nature Reviews Microbiology thanks Kevin Olival, Arvind Varsani and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Metagenomic next-generation sequencing

(mNGS). The parallel high-throughput sequencing of the total genetic material (RNA or DNA) extracted from a sample. This method offers scalability and speed that cannot be achieved by earlier sequencing technologies.

Virosphere

The total assemblage of RNA viruses and DNA viruses on Earth, infecting hosts of any type.

Viromes

Total assemblages of viruses in individual organisms or species.

Metatranscriptomics

The study of the total expressed RNA — the transcriptome — within a sample. The RNA can be derived from expressed host genes as well as microbial species within the host, including both RNA virsuses and DNA viruses.

Zoonotic disease

An infectious disease that can be transmitted from animals to humans.

Emergence

Process by which novel infectious diseases (or pathogens) appear in species or previously known diseases rapidly increase in incidence or geographical range. Often associated with cross-species transmission.

Metagenomics

The simultaneous sequencing of all genetic material within a sample, including all the microorganisms present. It can involve the analysis of individual marker genes such as 16S or 18S ribosomal RNA or complete genomes.

Co-divergence

Evolutionary pattern in which the phylogenetic history of a virus or other pathogen matches that of the host organisms on long evolutionary timescales.

Multicomponent viruses

Also referred to ‘multipartite viruses’. Viruses in which the genome segments are contained within separate virus particles. These are relatively commonplace in positive-sense RNA viruses of plants such as members of the Bromoviridae.

Genetic drift

The change in frequency of a mutation in a population due to the chance effect of random sampling. Although genetic drift occurs in all populations of finite size, its effect is strongest in small populations.

Cross-species transmission

Also referred to as ‘host-jumping’ or ‘host-switching’. The transmission of a virus from one host species to another.

Ectoparasites

Parasitic organisms that live on the skin of the host (rather than within a host), from which they derive their energy.

Spillover

The initial and sometimes transient appearance of a pathogen in a new species following a host jump. Can sometimes lead to a full-blown epidemic or pandemic.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Harvey, E., Holmes, E.C. Diversity and evolution of the animal virome. Nat Rev Microbiol 20, 321–334 (2022). https://doi.org/10.1038/s41579-021-00665-x

Download citation

  • Accepted:

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41579-021-00665-x

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing