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  • Review Article
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Revisiting the rules of life for viruses of microorganisms

Nature Reviews Microbiology volume 19, pages 501–513 (2021)Cite this article

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Abstract

Viruses that infect microbial hosts have traditionally been studied in laboratory settings with a focus on either obligate lysis or persistent lysogeny. In the environment, these infection archetypes are part of a continuum that spans antagonistic to beneficial modes. In this Review, we advance a framework to accommodate the context-dependent nature of virus–microorganism interactions in ecological communities by synthesizing knowledge from decades of virology research, eco-evolutionary theory and recent technological advances. We discuss that nuanced outcomes, rather than the extremes of the continuum, are particularly likely in natural communities given variability in abiotic factors, the availability of suboptimal hosts and the relevance of multitrophic partnerships. We revisit the ‘rules of life’ in terms of how long-term infections shape the fate of viruses and microbial cells, populations and ecosystems.

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Fig. 1: The viral infection continuum.
Fig. 2: Viral transmission strategies and ecological context.
Fig. 3: Examples of temperate phage–bacterium mutualisms.

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References

  1. Proctor, L. M. & Fuhrman, J. A. Viral mortality of marine bacteria and cyanobacteria. Nature 343, 60–62 (1990).

    Google Scholar 

  2. Bergh, O., Børsheim, K. Y., Bratbak, G. & Heldal, M. High abundance of viruses found in aquatic environments. Nature 340, 467–468 (1989).

    CAS  PubMed  Google Scholar 

  3. Cai, L. et al. Active and diverse viruses persist in the deep sub-seafloor sediments over thousands of years. ISME J. 13, 1857–1864 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Reyes, A., Semenkovich, N. P., Whiteson, K., Rohwer, F. & Gordon, J. I. Going viral: next-generation sequencing applied to phage populations in the human gut. Nat. Rev. Microbiol. 10, 607–617 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Fuhrman, J. A. Marine viruses and their biogeochemical and ecological effects. Nature 399, 541–548 (1999).

    CAS  PubMed  Google Scholar 

  6. Weinbauer, M. G. Ecology of prokaryotic viruses. FEMS Microbiol. Rev. 28, 127–181 (2004).

    CAS  PubMed  Google Scholar 

  7. Vega Thurber, R. L., Payet, J. P., Thurber, A. R. & Correa, A. M. S. Virus-host interactions and their roles in coral reef health and disease. Nat. Rev. Microbiol. 15, 205–216 (2017).

    Google Scholar 

  8. Zimmerman, A. E. et al. Metabolic and biogeochemical consequences of viral infection in aquatic ecosystems. Nat. Rev. Microbiol. 18, 21–34 (2020).

    CAS  PubMed  Google Scholar 

  9. Wilhelm, S. W. & Suttle, C. A. Viruses and nutrient cycles in the sea. Bioscience 49, 781–788 (1999). Seminal work modelling how viral activity in the oceans prevents up to a quarter of organic matter from being exported to higher trophic levels; instead, this matter is recycled (by viral lysis) into a form that can be assimilated by microorganisms.

    Google Scholar 

  10. Calendar, R. L. The Bacteriophages 2nd edn (Oxford University Press, 2005).

  11. Sullivan, M. B., Weitz, J. S. & Wilhelm, S. W. Viral ecology comes of age. Environ. Microbiol. Rep. 9, 33–35 (2017).

    PubMed  Google Scholar 

  12. Roux, S., Hallam, S. J., Woyke, T. & Sullivan, M. B. Viral dark matter and virus–host interactions resolved from publicly available microbial genomes. eLife 4, e08490 (2015).

    PubMed Central  Google Scholar 

  13. Paez-Espino, D. et al. Uncovering Earth’s virome. Nature 536, 425–430 (2016). An in silico catalogue of the diversity of viruses on Earth that serves as the foundation for the Joint Genome Institute’s growing IMG/VR database.

    CAS  PubMed  Google Scholar 

  14. Emerson, J. B. et al. Host-linked soil viral ecology along a permafrost thaw gradient. Nat. Microbiol. 3, 870–880 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Stough, J. M. A. et al. Diversity of active viral infections within the Sphagnum microbiome. Applied Environ. Microbiol. https://doi.org/10.1128/AEM.01124-18 (2018).

    Article  Google Scholar 

  16. Gregory, A. C. et al. Marine DNA viral macro- and microdiversity from pole to pole. Cell 177, 1109–1123.e1114 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. De Corte, D. et al. Viral communities in the global deep ocean conveyor belt assessed by targeted viromics. Front. Microbiol. https://doi.org/10.3389/fmicb.2019.01801 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  18. Jang, H. B. et al. Taxonomic assignment of uncultivated prokaryotic virus genomes is enabled by gene-sharing networks. Nat. Biotechnol. 37, 632–639 (2019).

    Google Scholar 

  19. Roux, S. A viral ecogenomics framework to uncover the secrets of nature’s “microbe whisperers”. mSystems 4, e00111–e00119 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Roux, S. et al. Minimum information about an uncultivated virus genome (MIUViG). Nat. Biotechnol. 37, 29 (2018).

    PubMed  PubMed Central  Google Scholar 

  21. Hobbs, Z. & Abedon, S. T. Diversity of phage infection types and associated terminology: the problem with ‘lytic or lysogenic’. FEMS Microbiol. Lett. https://doi.org/10.1093/femsle/fnw047 (2016).

    Article  PubMed  Google Scholar 

  22. Hay, I. D. & Lithgow, T. Filamentous phages: masters of a microbial sharing economy. EMBO Reports 20, e47427 (2019).

    PubMed  PubMed Central  Google Scholar 

  23. McLeod, S. M., Kimsey, H. H., Davis, B. M. & Waldor, M. K. CTXphi and Vibrio cholerae: exploring a newly recognized type of phage-host cell relationship. Mol. Microbiol. 57, 347–356 (2005).

    CAS  PubMed  Google Scholar 

  24. Howard-Varona, C. et al. Regulation of infection efficiency in a globally abundant marine Bacteriodetes virus. ISME J. 11, 284–295 (2017).

    CAS  PubMed  Google Scholar 

  25. Howard-Varona, C. et al. Multiple mechanisms drive phage infection efficiency in nearly identical hosts. ISME J. 12, 1605–1618 (2018).

    PubMed  PubMed Central  Google Scholar 

  26. Kirzner, S., Barak, E. & Lindell, D. Variability in progeny production and virulence of cyanophages determined at the single-cell level. Environ. Microbiol. Rep. 8, 605–613 (2016).

    PubMed  Google Scholar 

  27. Gregory, A. C. et al. Genomic differentiation among wild cyanophages despite widespread horizontal gene transfer. BMC Genomics 17, 930 (2016).

    PubMed  PubMed Central  Google Scholar 

  28. Holmfeldt, K. et al. Large‐scale maps of variable infection efficiencies in aquatic Bacteroidetes phage‐host model systems. Environ. Microbiol. 18, 3949–3961 (2016).

    CAS  PubMed  Google Scholar 

  29. Zborowsky, S. & Lindell, D. Resistance in marine cyanobacteria differs against specialist and generalist cyanophages. Proc. Natl Acad. Sci. USA https://doi.org/10.1073/pnas.1906897116 (2019). A meticulous investigation revealing that cyanobacteria defend against specialist phages by blocking their entry, whereas generalist phage infections are arrested intracellularly; thus generalist phages may be more common agents of horizontal gene transfer and co-infection.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Lwoff, A. Lysogeny. Bacteriol. Rev. 17, 269–337 (1953).

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Howard-Varona, C., Hargreaves, K. R., Abedon, S. T. & Sullivan, M. B. Lysogeny in nature: mechanisms, impact and ecology of temperate phages. ISME J. 11, 1511 (2017).

    PubMed  PubMed Central  Google Scholar 

  32. Abedon, S. T. The murky origin of Snow White and her T-even dwarfs. Genetics 155, 481–486 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Demerec, M. & Fano, U. Bacteriophage-resistant mutants in Escherichia coli. Genetics 30, 119–136 (1945).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Bronfenbrenner, J. J. & Korb, C. Studies on the bacteriophage of d’Herelle: I. Is the lytic principle volatile? J. Exp. Med. 41, 73–79 (1925).

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Kourilsky, P. & Knapp, A. Lysogenization by bacteriophage lambda: III. - Multiplicity dependent phenomena occuring upon infection by lambda. Biochimie 56, 1517–1523 (1975).

    Google Scholar 

  36. St-Pierre, F. & Endy, D. Determination of cell fate selection during phage lambda infection. Proc. Natl Acad. Sci. USA 105, 20705 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Zeng, L. et al. Decision making at a subcellular level determines the outcome of bacteriophage infection. Cell 141, 682–691 (2010). Re-examination of the phage λ decision switch via single-cell tracking of infection fates, revealing how increasing cellular multiplicity of infection increases the stochastic tendency towards lysogeny after infection.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Trinh, J. T., Székely, T., Shao, Q., Balázsi, G. & Zeng, L. Cell fate decisions emerge as phages cooperate or compete inside their host. Nat. Commun. 8, 14341 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Joh, R. I. & Weitz, J. S. To lyse or not to lyse: Transient-mediated stochastic fate determination in cells infected by bacteriophages. PLOS Comput. Biol. 7, e1002006 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Fillol-Salom, A. et al. Bacteriophages benefit from generalized transduction. PLOS Pathog. 15, e1007888 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Howard-Varona, C. et al. Fighting fire with fire: phage potential for the treatment of E. coli O157 infection. Antibiotics 7, 101 (2018).

    CAS  PubMed Central  Google Scholar 

  42. Pratama, A. A. & van Elsas, J. D. A novel inducible prophage from the mycosphere inhabitant Paraburkholderia terrae BS437. Sci. Rep. 7, 9156 (2017).

    PubMed  PubMed Central  Google Scholar 

  43. Jiang, S. C. & Paul, J. H. Seasonal and diel abundance of viruses and occurrence of lysogeny/bacteriocinogeny in the marine environment. Mar. Ecol. Prog. Ser. 104, 163–172 (1994).

    Google Scholar 

  44. Brum, J. R., Hurwitz, B. L., Schofield, O., Ducklow, H. W. & Sullivan, M. B. Seasonal time bombs: dominant temperate viruses affect Southern Ocean microbial dynamics. ISME J. 10, 437–449 (2016). Demonstration that lysogenic activity is favoured in low-productivity polar months (and lytic activity is favoured in high-productivity months), providing support for decades-old ecological hypotheses on the link between abiotic factors and viral strategies.

    CAS  PubMed  Google Scholar 

  45. Levin, R. A., Voolstra, C. R., Weynberg, K. D. & van Oppen, M. J. H. Evidence for a role of viruses in the thermal sensitivity of coral photosymbionts. ISME J. 11, 808–812 (2017).

    CAS  PubMed  Google Scholar 

  46. Vega Thurber, R. L. et al. Metagenomic analysis indicates that stressors induce production of herpes-like viruses in the coral Porites compressa. Proc. Natl Acad. Sci. USA 105, 18413–18418 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Correa, A. M. S. et al. Viral outbreak in corals associated with an in situ bleaching event: atypical herpes-like viruses and a new megavirus infecting Symbiodinium. Front. Microbiol. 7, 127 (2016).

    PubMed  PubMed Central  Google Scholar 

  48. Lawrence, S. A., Davy, J. E., Aeby, G. S., Wilson, W. H. & Davy, S. K. Quantification of virus-like particles suggests viral infection in corals affected by Porites tissue loss. Coral Reefs 33, 687–691 (2014).

    Google Scholar 

  49. Lawrence, S. A., Floge, S. A., Davy, J. E., Davy, S. K. & Wilson, W. H. Exploratory analysis of Symbiodinium transcriptomes reveals potential latent infection by large dsDNA viruses. Environ. Microbiol. 19, 3909–3919 (2017).

    CAS  PubMed  Google Scholar 

  50. Weynberg, K. D. et al. Prevalent and persistent viral infection in cultures of the coral algal endosymbiont Symbiodinium. Coral Reefs 36, 773–784 (2017).

    Google Scholar 

  51. Ptashne, M. et al. How the λ repressor and cro work. Cell 19, 1–11 (1980).

    CAS  PubMed  Google Scholar 

  52. Warwick-Dugdale, J., Buchholz, H. H., Allen, M. J. & Temperton, B. Host-hijacking and planktonic piracy: how phages command the microbial high seas. Virol. 16, 15 (2019).

    Google Scholar 

  53. Silpe, J. E. & Bassler, B. L. A host-produced quorum-sensing autoinducer controls a phage lysis-lysogeny decision. Cell 176, 268–280.e213 (2019).

    CAS  PubMed  Google Scholar 

  54. Erez, Z. et al. Communication between viruses guides lysis–lysogeny decisions. Nature 541, 488 (2017). Demonstration that viruses can ‘communicate’ to decide between lysis and lysogeny by co-opting a host system: extracellular release of small peptides.

    CAS  PubMed  PubMed Central  Google Scholar 

  55. Stokar-Avihail, A., Tal, N., Erez, Z., Lopatina, A. & Sorek, R. Widespread utilization of peptide communication in phages infecting soil and pathogenic bacteria. Cell Host Microbe 25, 746–755 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Ofir, G. & Sorek, R. Contemporary phage biology: from classic models to new insights. Cell 172, 1260–1270 (2018).

    CAS  PubMed  Google Scholar 

  57. McNamara, J. M. & Houston, A. I. State-dependent life histories. Nature 380, 215–221 (1996).

    CAS  PubMed  Google Scholar 

  58. Tan, D. et al. High cell densities favor lysogeny: induction of an H20 prophage is repressed by quorum sensing and enhances biofilm formation in Vibrio anguillarum. ISME J. 14, 1731–1742 (2020).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Pleška, M., Lang, M., Refardt, D., Levin, B. R. & Guet, C. C. Phage–host population dynamics promotes prophage acquisition in bacteria with innate immunity. Nat. Ecol. Evol 2, 359–366 (2018).

    PubMed  Google Scholar 

  60. Güemes, A. G. C. et al. Viruses as winners in the game of life. Annu. Rev. Virol. 3, 197–214 (2016).

    Google Scholar 

  61. Stewart, F. M. & Levin, B. R. The population biology of bacterial viruses: why be temperate. Theor. Popul. Biol. 26, 93–117 (1984). A seminal article that lays out key pressure points that should dictate temperate phage biology.

    CAS  PubMed  Google Scholar 

  62. Lipsitch, M., Siller, S. & Nowak, M. A. The evolution of virulence in pathogens with vertical and horizontal transmission. Evolution 50, 1729–1741 (1996).

    PubMed  Google Scholar 

  63. Frank, S. A. Models of parasite virulence. Q. Rev. Biol. 71, 37–78 (1996).

    CAS  PubMed  Google Scholar 

  64. Weitz, J. S., Li, G., Gulbudak, H., Cortez, M. H. & Whitaker, R. J. Viral invasion fitness across a continuum from lysis to latency. Virus Evol. https://doi.org/10.1093/ve/vez006 (2019). Theoretical study that examines the impact of ecological factors on the proliferation of viruses, enabled by a cell-centric (rather than a particle-centric) view of viral invasion fitness.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Li, G., Cortez, M. H., Dushoff, J. & Weitz, J. S. When to be temperate: on the fitness benefits of lysis vs. lysogeny. Virus Evol. https://doi.org/10.1093/ve/veaa042 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Berngruber, T. W., Froissart, R., Choisy, M. & Gandon, S. Evolution of virulence in emerging epidemics. PLOS Pathog. 9, e1003209 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Wahl, L. M., Betti, M. I., Dick, D. W., Pattenden, T. & Puccini, A. J. Evolutionary stability of the lysis-lysogeny decision: Why be virulent? Evolution 73, 92–98 (2019).

    CAS  PubMed  Google Scholar 

  68. Coy, S. R., Alsante, A. N., Van Etten, J. L. & Wilhelm, S. W. Cryopreservation of Paramecium bursaria Chlorella virus-1 during an active infection cycle of its host. PLoS ONE 14, e0211755 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. Godfrey-Smith, P. in Individuals Across the Sciences (eds Guay, A. & T. Pradeu, T.) (Oxford University Press, 2015).

  70. Forterre, P. The virocell concept and environmental microbiology. ISME J. 7, 233 (2013). Proposes the virocell concept, which argues that a given cell represents distinct entities when infected versus uninfected by a virus, providing a non-lytic mechanism by which viruses can significantly alter biogeochemical cycles.

    CAS  PubMed  Google Scholar 

  71. Rosenwasser, S., Ziv, C., van Creveld, S. G. & Vardi, A. Virocell metabolism: metabolic innovations during host-virus interactions in the ocean. Trends Microbiol. 24, 821–832 (2016).

    CAS  PubMed  Google Scholar 

  72. Howard-Varona, C. et al. Phage-specific metabolic reprogramming of virocells. ISME J. 14, 881–895 (2020).

    PubMed  PubMed Central  Google Scholar 

  73. Forterre, P. (ed.) Virocell Concept, The. In eLS https://doi.org/10.1002/9780470015902.a0023264 (2012).

  74. Diekmann, O., Heesterbeek, H. & Britton, T. Mathematical Tools for Understanding Infectious Disease Dynamics. 1st edn, 517 (Princeton University Press, 2012).

  75. Diekmann, O., Heesterbeek, J. A. P. & Metz, J. A. J. On the definition and the computation of the basic reproduction ratio R0 in models for infectious diseases in heterogeneous populations. J. Math. Biol. 28, 365–382 (1990).

    CAS  PubMed  Google Scholar 

  76. Diekmann, O., Heesterbeek, J. A. P. & Roberts, M. G. The construction of next-generation matrices for compartmental epidemic models. J. R. Soc. Interface 7, 873–885 (2010).

    CAS  PubMed  Google Scholar 

  77. van den Driessche, P. & Watmough, J. in Mathematical Epidemiology. Lecture Notes in Mathematics Vol. 1945 (eds Brauer, F., van den Driessche, P. & Wu, J.) 159–178 (Springer, 2008).

  78. Gandon, S., Day, T., Metcalf, C. J. E. & Grenfell, B. T. Forecasting epidemiological and evolutionary dynamics of infectious diseases. Trends Ecol. Evol. 31, 776–788 (2016).

    PubMed  Google Scholar 

  79. Roossinck, M. J. The good viruses: viral mutualistic symbioses. Nat. Rev. Microbiol. 9, 99–108 (2011).

    CAS  PubMed  Google Scholar 

  80. Bondy-Denomy, J. & Davidson, A. R. When a virus is not a parasite: the beneficial effects of prophages on bacterial fitness. J. Microbiol. 52, 235–242 (2014).

    CAS  PubMed  Google Scholar 

  81. Nanda, A. M., Thormann, K. & Frunzke, J. Impact of spontaneous prophage induction on the fitness of bacterial populations and host-microbe interactions. J. Bacteriol. 197, 410 (2015).

    PubMed  PubMed Central  Google Scholar 

  82. Obeng, N., Pratama, A. A. & Elsas, J. D. V. The significance of mutualistic phages for bacterial ecology and evolution. Trends Microbiol. 24, 440–449 (2016).

    CAS  PubMed  Google Scholar 

  83. Hutchinson, G. E. Concluding remarks. Cold Spring Harb. Symposia Quant. Biol. 22, 415–427 (1957).

    Google Scholar 

  84. Taylor, V. L., Fitzpatrick, A. D., Islam, Z. & Maxwell, K. L. The diverse impacts of phage morons on bacterial fitness and virulence. Adv. Virus Res. 103, 1–31 (2019).

    CAS  PubMed  Google Scholar 

  85. Hendrix, R. W., Lawrence, J. G., Hatfull, G. F. & Casjens, S. The origins and ongoing evolution of viruses. Trends Microbiol. 8, 504–508 (2000).

    CAS  PubMed  Google Scholar 

  86. Casjens, S. R. & Hendrix, R. W. Bacteriophage lambda: early pioneer and still relevant. Virology 479-480, 310–330 (2015).

    CAS  PubMed  Google Scholar 

  87. Fortier, L. C. & Sekulovic, O. Importance of prophages to evolution and virulence of bacterial pathogens. Virulence 4, 354–365 (2013).

    PubMed  PubMed Central  Google Scholar 

  88. Harrison, E. & Brockhurst, M. A. Ecological and evolutionary benefits of temperate phage: what does or doesn’t kill you makes you stronger. BioEssays 39, 1700112 (2017).

    Google Scholar 

  89. Berngruber, T. W., Weissing, F. J. & Gandon, S. Inhibition of superinfection and the evolution of viral latency. J. Virol. 4, 10200–10208 (2010).

    Google Scholar 

  90. Susskind, M. M., Botstein, D. & Wright, A. Superinfection exclusion by P22 prophage in lysogens of Salmonella typhimurium: III. Failure of superinfecting phage DNA to enter sieA+ lysogens. Virology 62, 350–366 (1974).

    CAS  PubMed  Google Scholar 

  91. van Houte, S., Buckling, A. & Westra, E. R. Evolutionary ecology of prokaryotic immune mechanisms. Microbiol. Mol. Biol. Rev. 80, 745 (2016).

    PubMed  PubMed Central  Google Scholar 

  92. Dodd, I. B., Shearwin, K. E. & Egan, J. B. Revisited gene regulation in bacteriophage lambda. Curr. Opin. Genet. Dev. 15, 145–152 (2005).

    CAS  PubMed  Google Scholar 

  93. Díaz-Muñoz, S. L. Viral coinfection is shaped by host ecology and virus-virus interactions across diverse microbial taxa and environments. Virus Evol. 3, vex011 (2017).

    PubMed  PubMed Central  Google Scholar 

  94. Breitbart, M., Bonnain, C., Malki, K. & Sawaya, N. A. Phage puppet masters of the marine microbial realm. Nat. Microbiol. 3, 754–766 (2018).

    CAS  PubMed  Google Scholar 

  95. Knowles, B. et al. Lytic to temperate switching of viral communities. Nature 531, 466–470 (2016).

    CAS  PubMed  Google Scholar 

  96. Weitz, J. S., Beckett, S. J., Brum, J. R., Cael, B. B. & Dushoff, J. Lysis, lysogeny and virus-microbe ratios. Nature 549, E1–E3 (2017).

    CAS  PubMed  Google Scholar 

  97. Knowles, B. & Rohwer, F. Knowles & Rohwer reply. Nature 549, E3–E4 (2017).

    CAS  PubMed  Google Scholar 

  98. Wagner, P. L. & Waldor, M. K. Bacteriophage control of bacterial virulence. Infect. Immun. 70, 3985–3993 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  99. Erickson, A. K. et al. Bacteria facilitate enteric virus co-infection of mammalian cells and promote genetic recombination. Cell Host Microbe 23, 77–88.e75 (2018).

    CAS  PubMed  Google Scholar 

  100. Davies, E. V., Winstanley, C., Fothergill, J. L. & James, C. E. The role of temperate bacteriophages in bacterial infection. FEMS Microbiol. Lett. https://doi.org/10.1093/femsle/fnw015 (2016).

    Article  PubMed  Google Scholar 

  101. Schroven, K., Aertsen, A. & Lavigne, R. Bacteriophages as drivers of bacterial virulence and their potential for biotechnological exploitation. FEMS Microbiol. Rev. https://doi.org/10.1093/femsre/fuaa041 (2020).

    Article  Google Scholar 

  102. Waldor, M. K. & Mekalanos, J. J. Lysogenic conversion by a filamentous phage encoding cholera toxin. Science 272, 1910–1914 (1996).

    CAS  PubMed  Google Scholar 

  103. Matsuda, M. & Barksdale, L. Phage-directed synthesis of diphtherial toxin in non-toxinogenic Corynebacterium diphtheriae. Nature 210, 911–913 (1966).

    CAS  PubMed  Google Scholar 

  104. O’Brien, A. D. et al. Shiga-like toxin-converting phages from Escherichia coli strains that cause hemorrhagic colitis or infantile diarrhea. Science 226, 694 (1984).

    PubMed  Google Scholar 

  105. Gerlach, D. et al. Methicillin-resistant Staphylococcus aureus alters cell wall glycosylation to evade immunity. Nature 563, 705–709 (2018).

    CAS  PubMed  Google Scholar 

  106. Jahn, M. T. et al. A phage protein aids bacterial symbionts in eukaryote immune evasion. Cell Host Microbe 26, 542–550.e545 (2019).

    CAS  PubMed  Google Scholar 

  107. Weynberg, K. D., Voolstra, C. R., Neave, M. J., Buerger, P. & Van Oppen, M. J. H. From cholera to corals: Viruses as drivers of virulence in a major coral bacterial pathogen. Sci. Rep. 5, 17889 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  108. Menouni, R., Hutinet, G., Petit, M. A. & Ansaldi, M. Bacterial genome remodeling through bacteriophage recombination. FEMS Microbiol. Lett. 362, 1–10 (2015).

    CAS  PubMed  Google Scholar 

  109. Feiner, R. et al. A new perspective on lysogeny: prophages as active regulatory switches of bacteria. Nat. Rev. Microbiol. 13, 641–650 (2015).

    CAS  PubMed  Google Scholar 

  110. Duerkop, B. A., Clements, C. V., Rollins, D., Rodrigues, J. L. M. & Hooper, L. V. A composite bacteriophage alters colonization by an intestinal commensal bacterium. Proc. Natl Acad. Sci. USA 109, 17621–17626 (2012). Demonstrates that temperate virus infections (including those derived from distinct, spatially separated prophage elements) can ‘make winners’ out of their hosts by providing the hosts with competitive advantages.

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Gama, J. A. et al. Temperate bacterial viruses as double-edged swords in bacterial warfare. PLoS ONE https://doi.org/10.1371/journal.pone.0059043 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  112. Davies, E. V. et al. Temperate phages enhance pathogen fitness in chronic lung infection. ISME J. 10, 2553–2555 (2016).

    PubMed  PubMed Central  Google Scholar 

  113. Bossi, L., Fuentes, J. A., Mora, G. & Figueroa-Bossi, N. Prophage contribution to bacterial population dynamics. J. Bacteriol. 185, 6467–6471 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  114. Basso, J. T. R. et al. Genetically similar temperate phages form coalitions with their shared host that lead to niche-specific fitness effects. ISME J. 14, 1688–1700 (2020). Demonstrates that two genetically similar, but incompatible, temperate phages that lysogenize the same Roseobacter host can impart distinct physiological traits on that host; thus, each makes its host ‘the winner’ under different environmental conditions.

    CAS  PubMed  PubMed Central  Google Scholar 

  115. Li, X. Y. et al. Temperate phages as self-replicating weapons in bacterial competition. J. R. Soc. Interface https://doi.org/10.1098/rsif.2017.0563 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  116. Weitz, J. S. et al. Phage-bacteria infection networks. Trends Microbiol. 21, 82–91 (2013).

    CAS  PubMed  Google Scholar 

  117. Dang, V., Howard-Varona, C., Schwenck, S. & Sullivan, M. B. Variably lytic infection dynamics of large Bacteroidetes podovirus phi38:1 against two Cellulophaga baltica host strains. Environ. Microbiol. 17, 4659–4671 (2015).

    CAS  PubMed  Google Scholar 

  118. Holmfeldt, K., Howard-Varona, C., Solonenko, N. & Sullivan, M. B. Contrasting genomic patterns and infection strategies of two co-existing Bacteroidetes podovirus genera. Environ. Microbiol. 16, 2501–2513 (2014).

    CAS  PubMed  Google Scholar 

  119. Flores, C. O., Meyer, J. R., Valverde, S., Farr, L. & Weitz, J. S. Statistical structure of host–phage interactions. Proc. Natl Acad. Sci. USA 108, E288–E297 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. Parmar, K. M., Gaikwad, S. L., Dhakephalkar, P. K., Kothari, R. & Singh, R. P. Intriguing interaction of bacteriophage-host association: an understanding in the era of omics. Front. Microbiol. 8, 559 (2017).

    PubMed  PubMed Central  Google Scholar 

  121. Flores, C. O., Valverde, S. & Weitz, J. S. Multi-scale structure and geographic drivers of cross-infection within marine bacteria and phages. ISME J. 7, 520 (2012).

    PubMed  PubMed Central  Google Scholar 

  122. Koskella, B. & Meaden, S. Understanding bacteriophage specificity in natural microbial communities. Viruses 5, 806–823 (2013).

    PubMed  PubMed Central  Google Scholar 

  123. Roux, S. et al. Ecology and evolution of viruses infecting uncultivated SUP05 bacteria as revealed by single-cell- and meta- genomics. eLife https://doi.org/10.7554/eLife.03125 (2014).

    Article  PubMed  PubMed Central  Google Scholar 

  124. Labonte, J. M. et al. Single-cell genomics-based analysis of virus-host interactions in marine surface bacterioplankton. ISME J. 9, 2386–2399 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. Munson-McGee, J. H. et al. A virus or more in (nearly) every cell: ubiquitous networks of virus-host interactions in extreme environments. ISME J. 12, 1706–1714 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  126. Díaz-Muñoz, S. L., Sanjuán, R. & West, S. Sociovirology: conflict, cooperation, and communication among viruses. Cell Host Microbe 22, 437–441 (2017).

    PubMed  PubMed Central  Google Scholar 

  127. Landsberger, M. et al. Anti-CRISPR phages cooperate to overcome CRISPR-Cas immunity. Cell 174, 908 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  128. Kieft, K., Zhou, Z. & Anantharaman, K. VIBRANT: automated recovery, annotation and curation of microbial viruses, and evaluation of viral community function from genomic sequences. Microbiome 8, 90 (2020).

    PubMed  PubMed Central  Google Scholar 

  129. Coutinho, F. H. et al. Marine viruses discovered via metagenomics shed light on viral strategies throughout the oceans. Nat. Commun. https://doi.org/10.1038/ncomms15955 (2017).

    Article  PubMed  PubMed Central  Google Scholar 

  130. Alrasheed, H., Jin, R. & Weitz, J. S. Caution in inferring viral strategies from abundance correlations in marine metagenomes. Nat. Commun. 10, 501 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  131. Roossinck, M. J. Metagenomics of plant and fungal viruses reveals an abundance of persistent lifestyles. Front.Microbiol. https://doi.org/10.3389/fmicb.2014.00767 (2015).

    Article  PubMed  PubMed Central  Google Scholar 

  132. Bordenstein, S. R. & Bordenstein, S. R. Eukaryotic association module in phage WO genomes from Wolbachia. Nat. Commun. 7, 13155 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  133. Gilmore, M. S. & Miller, O. K. A bacterium’s enemy isn’t your friend. Nature 563, 637–638 (2018).

    CAS  PubMed  Google Scholar 

  134. Callanan, J. et al. RNA phage biology in a metagenomic era. Viruses 10, 386 (2018).

    PubMed Central  Google Scholar 

  135. Dion, M. B., Oechslin, F. & Moineau, S. Phage diversity, genomics and phylogeny. Nat. Rev. Microbiol. 18, 125–138 (2020).

    CAS  PubMed  Google Scholar 

  136. Ross, A., Ward, S. & Hyman, P. More is better: Selecting for broad host range bacteriophages. Front. Microbiol. https://doi.org/10.3389/fmicb.2016.01352 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  137. de Jonge, P. A. et al. Adsorption sequencing as a rapid method to link environmental bacteriophages to hosts. iScience https://doi.org/10.1016/j.isci.2020.101439 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  138. Deng, L. et al. Viral tagging reveals discrete populations in Synechococcus viral genome sequence space. Nature 513, 242–245 (2014).

    CAS  PubMed  Google Scholar 

  139. Džunková, M. et al. Defining the human gut host–phage network through single-cell viral tagging. Nat. Microbiol. https://doi.org/10.1038/s41564-019-0526-2 (2019).

    Article  PubMed  Google Scholar 

  140. Labonte, J. M. et al. Single cell genomics-based analysis of gene content and expression of prophages in a diffuse-flow deep-sea hydrothermal system. Front.Microbiol. https://doi.org/10.3389/fmicb.2019.01262 (2019).

    Article  PubMed  PubMed Central  Google Scholar 

  141. Edwards, R. A., McNair, K., Faust, K., Raes, J. & Dutilh, B. E. Computational approaches to predict bacteriophage-host relationships. FEMS Microbiol. Rev. 40, 258–272 (2016).

    CAS  PubMed  Google Scholar 

  142. Jover, L. F., Romberg, J. & Weitz, J. S. Inferring phage–bacteria infection networks from time-series data. R. Soc. Open Sci. 3, 160654 (2016).

    PubMed  PubMed Central  Google Scholar 

  143. Woodcroft, B. J. et al. Genome-centric view of carbon processing in thawing permafrost. Nature 560, 49–54 (2018).

    CAS  PubMed  Google Scholar 

  144. Nayfach, S., Shi, Z. J., Seshadri, R., Pollard, K. S. & Kyrpides, N. C. New insights from uncultivated genomes of the global human gut microbiome. Nature 568, 505–510 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  145. Almeida, A. et al. A new genomic blueprint of the human gut microbiota. Nature 568, 499–504 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  146. Pasolli, E. et al. Extensive unexplored human microbiome diversity revealed by over 150,000 genomes from metagenomes spanning age, geography, and lifestyle. Cell 176, 649–662.e620 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  147. Tully, B. J., Graham, E. D. & Heidelberg, J. F. The reconstruction of 2,631 draft metagenome-assembled genomes from the global oceans. Sci. Data 5, 170203 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  148. Mihara, T. et al. Linking virus genomes with host taxonomy. Viruses 8, 66 (2016).

    PubMed  PubMed Central  Google Scholar 

  149. Laffy, P. W. et al. HoloVir: a workflow for investigating the diversity and function of viruses in invertebrate holobionts. Front. Microbiol. https://doi.org/10.3389/fmicb.2016.00822 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  150. Bolduc, B., Youens-Clark, K., Roux, S., Hurwitz, B. L. & Sullivan, M. B. iVirus: facilitating new insights into viral ecology with software and community datasets imbedded in a cyberinfrastructure. ISME J. 11, 7–14 (2017).

    PubMed  Google Scholar 

  151. Baran, N., Goldin, S., Maidanik, I. & Lindell, D. Quantification of diverse virus populations in the environment using the polony method. Nat. Microbiol. 3, 62–72 (2018).

    CAS  PubMed  Google Scholar 

  152. Mruwat, N. et al. A single-cell polony method reveals low levels of infected Prochlorococcus in oligotrophic waters despite high cyanophage abundances. ISME J. (2020).

  153. Martínez-García, M., Santos, F., Moreno-Paz, M., Parro, V. & Antón, J. Unveiling viral–host interactions within the ‘microbial dark matter’. Nat. Commun. 5, 4542 (2014).

    PubMed  Google Scholar 

  154. Spencer, S. J. et al. Massively parallel sequencing of single cells by epicPCR links functional genes with phylogenetic markers. ISME J. 10, 427–436 (2016).

    CAS  PubMed  Google Scholar 

  155. Bickhart, D. M. et al. Assignment of virus and antimicrobial resistance genes to microbial hosts in a complex microbial community by combined long-read assembly and proximity ligation. Genome Biol. 20, 153 (2019).

    PubMed  PubMed Central  Google Scholar 

  156. Marbouty, M., Baudry, L., Cournac, A. & Koszul, R. Scaffolding bacterial genomes and probing host-virus interactions in gut microbiome by proximity ligation (chromosome capture) assay. Sci. Adv. 3, e1602105 (2017).

    PubMed  PubMed Central  Google Scholar 

  157. Lopez-Madrigal, S., Latorre, A., Porcar, M., Moya, A. & Gil, R. Mealybugs nested endosymbiosis: going into the ‘matryoshka’ system in Planococcus citri in depth. BMC Microbiol. https://doi.org/10.1186/1471-2180-13-74 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  158. Noda, S. et al. Cospeciation in the triplex symbiosis of termite gut protists (Pseudotrichonympha spp.), their hosts, and their bacterial endosymbionts. Mol. Ecol. 16, 1257–1266 (2007).

    CAS  PubMed  Google Scholar 

  159. Woyke, T. & Schulz, F. Entities inside one another - a matryoshka doll in biology? Environ. Microbiol. Rep. 11, 26–28 (2019).

    PubMed  Google Scholar 

  160. Chatterjee, A. & Duerkop, B. A. Beyond bacteria: Bacteriophage-eukaryotic host interactions reveal emerging paradigms of health and disease. Front. Microbiol. https://doi.org/10.3389/fmicb.2018.01394 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  161. Bordenstein, S. R., Marshall, M. L., Fry, A. J., Kim, U. & Wernegreen, J. J. The tripartite associations between bacteriophage, Wolbachia, and arthropods. PLOS Pathog. 2, e43 (2006).

    PubMed  PubMed Central  Google Scholar 

  162. Shropshire, J. D., On, J., Layton, E. M., Zhou, H. & Bordenstein, S. R. One prophage WO gene rescues cytoplasmic incompatibility in Drosophila melanogaster. Proc. Natl Acad. Sci. USA 115, 4987 (2018). One of the genes in Wolbachia-infecting prophage WO that was previously shown to induce cytoplasmic incompatibility (in combination with a second gene) in insect gametes is demonstrated to also independently rescue cytoplasmic incompatibility and nullify associated embryonic defects.

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Beckmann, J. F. et al. The toxin–antidote model of cytoplasmic incompatibility: Genetics and evolutionary implications. Trends Genet. 35, 175–185 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  164. Sweere, J. M. et al. Bacteriophage trigger antiviral immunity and prevent clearance of bacterial infection. Science 363, eaat9691 (2019).

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Marquez, L. M., Redman, R. S., Rodriguez, R. J. & Roossinck, M. J. A virus in a fungus in a plant: Three-way symbiosis required for thermal tolerance. Science 315, 513–515 (2007). An early example of a mutualistic ‘nested’ symbiosis involving viruses; in this case, the direct fungal host of a virus as well as the plant host of the fungus benefitted from viral infection.

    CAS  PubMed  Google Scholar 

  166. van Oppen, M. J. H., Leong, J.-A. & Gates, R. D. Coral-virus interactions: a double-edged sword? Symbiosis 47, 1–8 (2009).

    Google Scholar 

  167. Tikhe, C. V. & Husseneder, C. Metavirome sequencing of the termite gut reveals the presence of an unexplored bacteriophage community. Front. Microbiol. https://doi.org/10.3389/fmicb.2017.02548 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Stimulating discussions at a Canadian Institute for Advanced Research–Gordon and Betty Moore Foundation workshop entitled “Continuum of Persistence – Ecology and Function of Persistent Virus Infections” contributed to the initial motivation for and direction of this work. An American Association for the Advancement of Science (AAAS) special session entitled “Viruses, Microbes and Their Entangled Fates” facilitated discussions and ultimately led to this Review, and AAAS is acknowledged for travel support provided to A.M.S.C. Funding that supported this synthesis was provided by the NSF Biological Oceanography Program (OCE#1635798 and OCE#1928609 to A.M.S.C., OCE#1829831 to M.B.S., OCE#1829640 to M.B.S. and OCE#1829636 to J.S.W. and OCE#1737237 to A.B.), an Early-Career Research Fellowship (#2000009651) from the Gulf Research Program of the US National Academies of Sciences to A.M.S.C., the Gordon and Betty Moore Foundation (#3790 to M.B.S.) and the Simons Foundation (SCOPE Award ID 329108 and Award ID 722153 to J.S.W and Award ID 735083 to A.B.).

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Authors and Affiliations

  1. BioSciences Department, Rice University, Houston, TX, USA

    Adrienne M. S. Correa & Samantha R. Coy

  2. Department of Microbiology, The Ohio State University, Columbus, OH, USA

    Cristina Howard-Varona & Matthew B. Sullivan

  3. Department of Microbiology, University of Tennessee, Knoxville, TN, USA

    Alison Buchan

  4. Department of Civil, Environmental, and Geodetic Engineering, The Ohio State University, Columbus, OH, USA

    Matthew B. Sullivan

  5. School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA, USA

    Joshua S. Weitz

  6. School of Physics, Georgia Institute of Technology, Atlanta, GA, USA

    Joshua S. Weitz

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  4. Alison Buchan
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A.M.S.C., A.B., M.B.S. and J.S.W. conceptualized the Review. All authors contributed to all aspects of manuscript development, including research, writing and editing.

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Glossary

Viral shunt

Prevention of dissolved and particulate carbon from being incorporated into consumers at higher trophic levels due to the release of this carbon from infected host cells via viral lysis.

Lytic infections

Infections involving the reproduction of viral genetic material, packing of viral genetic material into capsids and release of virus particles into the environment following the lysis (that is, rupture) and death of the host cell.

Bacteriophages (or phages)

Viruses that exclusively infect bacterial cells.

Lysogenic infections

A viral infection state in which the viral genome is integrated into that of the host cellular genome and can be replicated during division without lysing the cell.

Chronic infections

Infections in which viral progeny are released from the host cell into the environment but lysis and death of that infected cell do not necessarily occur.

Inefficient lytic infections

Infections by a virulent virus that may be stalled or terminated at one or multiple stages of the infection cycle, from adsorption to the host cell through to cell lysis.

Latent infection

A state of reduced lytic activity, which includes lysogeny (that is, the viral genome is integrated into the host genome), chronic infection and other infection states (including otherwise lytic viruses that infect hosts during non-optimal conditions).

Temperate phages

Viruses that can establish a lytic cycle or a lysogenic cycle.

Prophage

An integrated genome of a temperate phage inside a lysogen.

Cellular multiplicity of infection

The discrete number of viruses that have infected a given cell. ‘Cellular multiplicity of infection’ is distinct from the commonly used term ‘multiplicity of infection’ (that is, the population-level ratio of the number of virus particles to the number of cells).

Adsorption

Viral attachment to a host cell.

Lysogens

Cells with a prophage, which is either integrated into the cellular genome or is extrachromosomal.

Virocell

A cell infected by a virus that reshapes cellular physiology so that it is controlled by viral genetic programmes.

Heteroimmunity

Denoting when two phages have heterotypic (unrelated) genetic elements (that is, repressor and cognate operator) to control the lytic cycle and, as a consequence, neither prophage is able to prevent infection of the host by the other virus.

Superinfection

Viral infection of a cell harbouring another virus.

Cytoplasmic incompatibility

Caused by maternally inherited bacteria, a situation in which factors in the cytoplasm of two gametes are not compatible, preventing the formation of viable offspring.

Co-infection

The simultaneous infection of a cell by more than one virus; the viruses need not be closely related.

Homoimmunity

Denoting when a prophage confers immunity against infection by similar viruses because both the resident prophage and the incoming virus contain homotypic (identical or nearly identical) genetic elements (that is, repressor and cognate operator) to control the lytic cycle.

Carrier states

Cells that are considered to have a chronic infection.

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Correa, A.M.S., Howard-Varona, C., Coy, S.R. et al. Revisiting the rules of life for viruses of microorganisms. Nat Rev Microbiol 19, 501–513 (2021). https://doi.org/10.1038/s41579-021-00530-x

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