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Journal of General Virology header logo Journal of General Virology

Volume 103, Issue 6

Embracing the heterogeneity of natural viruses in mouse studies Open Access

Abstract

Animal models are a critical tool in modern biology. To increase reproducibility and to reduce confounding variables modern animal models exclude many microbes, including key natural commensals and pathogens. Here we discuss recent strategies to incorporate a natural microbiota to laboratory mouse models and the impacts the microbiota has on immune responses, with a focus on viruses.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): dirty mice , microbiome and virome
Funding
This study was supported by the:
  • University of Minnesota McKnight Foundation (Award N.A.)
    • Principle Award Recipient: RyanA. Langlois
  • Foundation for the National Institutes of Health (Award AI50600)
    • Principle Award Recipient: RyanA. Langlois
© 2022 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2022-06-23
2025-04-22
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References

  1. Masopust D, Sivula CP, Jameson SC. Of mice, dirty mice, and men: using mice to understand human immunology. J Immunol 2017; 199:383–388 [View Article] [PubMed]
     [Google Scholar]
  2. Williams SH, Che X, Garcia JA, Klena JD, Lee B et al. Viral diversity of house mice in New York City. mBio 2018; 9:e01354-17 [View Article] [PubMed]
     [Google Scholar]
  3. Suntharalingam G, Perry MR, Ward S, Brett SJ, Castello-Cortes A et al. Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412. N Engl J Med 2006; 355:1018–1028 [View Article] [PubMed]
     [Google Scholar]
  4. Fisher CJ, Agosti JM, Opal SM, Lowry SF, Balk RA et al. Treatment of septic shock with the tumor necrosis factor receptor:Fc fusion protein. N Engl J Med 1996; 334:1697–1702 [View Article] [PubMed]
     [Google Scholar]
  5. Lim ES, Zhou Y, Zhao G, Bauer IK, Droit L et al. Early life dynamics of the human gut virome and bacterial microbiome in infants. Nat Med 2015; 21:1228–1234 [View Article] [PubMed]
     [Google Scholar]
  6. Liang G, Zhao C, Zhang H, Mattei L, Sherrill-Mix S et al. The stepwise assembly of the neonatal virome is modulated by breastfeeding. Nature 2020; 581:470–474 [View Article] [PubMed]
     [Google Scholar]
  7. Kim AH, Armah G, Dennis F, Wang L, Rodgers R et al. Enteric virome negatively affects seroconversion following oral rotavirus vaccination in a longitudinally sampled cohort of Ghanaian infants. Cell Host Microbe 2022; 30:110–123 [View Article] [PubMed]
     [Google Scholar]
  8. Zhang C, Burch M, Wylie K, Herter B, Franklin CL et al. Characterization of the eukaryotic virome of mice from different sources. Microorganisms 2021; 9:2064 [View Article] [PubMed]
     [Google Scholar]
  9. Fay EJ, Balla KM, Roach SN, Shepherd FK, Putri DS et al. Natural rodent model of viral transmission reveals biological features of virus population dynamics. J Exp Med 2022; 219:e20211220 [View Article]
     [Google Scholar]
  10. Phan TG, Kapusinszky B, Wang C, Rose RK, Lipton HL et al. The fecal viral flora of wild rodents. PLoS Pathog 2011; 7:e1002218 [View Article] [PubMed]
     [Google Scholar]
  11. Kernbauer E, Ding Y, Cadwell K. An enteric virus can replace the beneficial function of commensal bacteria. Nature 2014; 516:94–98 [View Article] [PubMed]
     [Google Scholar]
  12. Ingle H, Lee S, Ai T, Orvedahl A, Rodgers R et al. Viral complementation of immunodeficiency confers protection against enteric pathogens via interferon-λ. Nat Microbiol 2019; 4:1120–1128 [View Article] [PubMed]
     [Google Scholar]
  13. Liu L, Gong T, Tao W, Lin B, Li C et al. Commensal viruses maintain intestinal intraepithelial lymphocytes via noncanonical RIG-I signaling. Nat Immunol 2019; 20:1681–1691 [View Article] [PubMed]
     [Google Scholar]
  14. Broggi A, Tan Y, Granucci F, Zanoni I. IFN-λ suppresses intestinal inflammation by non-translational regulation of neutrophil function. Nat Immunol 2017; 18:1084–1093 [View Article] [PubMed]
     [Google Scholar]
  15. Yang JY, Kim MS, Kim E, Cheon JH, Lee YS et al. Enteric viruses ameliorate gut inflammation via toll-like receptor 3 and toll-like receptor 7-mediated interferon-β production. Immunity 2016; 44:889–900 [View Article] [PubMed]
     [Google Scholar]
  16. Dallari S, Heaney T, Rosas-Villegas A, Neil JA, Wong SY et al. Enteric viruses evoke broad host immune responses resembling those elicited by the bacterial microbiome. Cell Host Microbe 2021; 29:1014–1029 [View Article] [PubMed]
     [Google Scholar]
  17. Dumortier J, Streblow DN, Moses AV, Jacobs JM, Kreklywich CN et al. Human cytomegalovirus secretome contains factors that induce angiogenesis and wound healing. J Virol 2008; 82:6524–6535 [View Article] [PubMed]
     [Google Scholar]
  18. Oberstein A, Shenk T. Cellular responses to human cytomegalovirus infection: Induction of a mesenchymal-to-epithelial transition (MET) phenotype. Proc Natl Acad Sci U S A 2017; 114:E8244–E8253 [View Article] [PubMed]
     [Google Scholar]
  19. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest 2009; 119:1420–1428 [View Article] [PubMed]
     [Google Scholar]
  20. Streblow DN, Dumortier J, Moses AV, Orloff SL, Nelson JA. Mechanisms of cytomegalovirus-accelerated vascular disease: induction of paracrine factors that promote angiogenesis and wound healing. Curr Top Microbiol Immunol 2008; 325:397–415 [View Article] [PubMed]
     [Google Scholar]
  21. Fischer JC, Bscheider M, Eisenkolb G, Lin C-C, Wintges A et al. RIG-I/MAVS and STING signaling promote gut integrity during irradiation- and immune-mediated tissue injury. Sci Transl Med 2017; 9:eaag2513 [View Article] [PubMed]
     [Google Scholar]
  22. Bouziat R, Hinterleitner R, Brown JJ, Stencel-Baerenwald JE, Ikizler M et al. Reovirus infection triggers inflammatory responses to dietary antigens and development of celiac disease. Science 2017; 356:44–50 [View Article] [PubMed]
     [Google Scholar]
  23. Glass RI, Parashar UD, Estes MK. Norovirus gastroenteritis. N Engl J Med 2009; 361:1776–1785 [View Article] [PubMed]
     [Google Scholar]
  24. Cadwell K, Patel KK, Maloney NS, Liu T-C, Ng ACY et al. Virus-plus-susceptibility gene interaction determines Crohn’s disease gene Atg16L1 phenotypes in intestine. Cell 2010; 141:1135–1145 [View Article] [PubMed]
     [Google Scholar]
  25. Liao JB. Viruses and human cancer. Yale J Biol Med 2006; 79:115–122 [PubMed]
     [Google Scholar]
  26. Tempera I, Lieberman PM. Oncogenic viruses as entropic drivers of cancer evolution. Front Virol 2021; 1:753366 [View Article] [PubMed]
     [Google Scholar]
  27. Singleton GR, Smith AL, Krebs CJ. The prevalence of viral antibodies during a large population fluctuation of house mice in Australia. Epidemiol Infect 2000; 125:719–727 [View Article] [PubMed]
     [Google Scholar]
  28. Becker SD, Bennett M, Stewart JP, Hurst JL. Serological survey of virus infection among wild house mice (Mus domesticus) in the UK. Lab Anim 2007; 41:229–238 [View Article] [PubMed]
     [Google Scholar]
  29. Morita C, Matsuura Y, Kawashima E, Takahashi S, Kawaguchi J et al. Seroepidemiological survey of lymphocytic choriomeningitis virus in wild house mouse (Mus musculus) in Yokohama Port, Japan. J Vet Med Sci 1991; 53:219–222 [View Article] [PubMed]
     [Google Scholar]
  30. Moro D, Lloyd ML, Smith AL, Shellam GR, Lawson MA. Murine viruses in an island population of introduced house mice and endemic short-tailed mice in Western Australia. J Wildl Dis 1999; 35:301–310 [View Article] [PubMed]
     [Google Scholar]
  31. Smith AL, Singleton GR, Hansen GM, Shellam G. A serologic survey for viruses and Mycoplasma pulmonis among wild house mice (Mus domesticus) in southeastern Australia. J Wildl Dis 1993; 29:219–229 [View Article] [PubMed]
     [Google Scholar]
  32. Williams SH, Che X, Oleynik A, Garcia JA, Muller D et al. Discovery of two highly divergent negative-sense RNA viruses associated with the parasitic nematode, Capillaria hepatica, in wild Mus musculus from New York City. J Gen Virol 2019; 100:1350–1362 [View Article] [PubMed]
     [Google Scholar]
  33. Abolins S, Lazarou L, Weldon L, Hughes L, King EC et al. The ecology of immune state in a wild mammal, Mus musculus domesticus. PLoS Biol 2018; 16:e2003538 [View Article] [PubMed]
     [Google Scholar]
  34. Lochmiller RL, Vestey MR, McMurry ST. Primary immune responses of selected small mammal species to heterologous erythrocytes. Comp Biochem Physiol A Comp Physiol 1991; 100:139–143 [View Article] [PubMed]
     [Google Scholar]
  35. Abolins SR, Pocock MJO, Hafalla JCR, Riley EM, Viney ME. Measures of immune function of wild mice, Mus musculus. Mol Ecol 2011; 20:881–892 [View Article] [PubMed]
     [Google Scholar]
  36. Abolins S, King EC, Lazarou L, Weldon L, Hughes L et al. The comparative immunology of wild and laboratory mice, Mus musculus domesticus. Nat Commun 2017; 8:14811 [View Article] [PubMed]
     [Google Scholar]
  37. Boysen P, Eide DM, Storset AK. Natural killer cells in free-living Mus musculus have a primed phenotype. Mol Ecol 2011; 20:5103–5110 [View Article] [PubMed]
     [Google Scholar]
  38. Devalapalli AP, Lesher A, Shieh K, Solow JS, Everett ML et al. Increased levels of IgE and autoreactive, polyreactive IgG in wild rodents: implications for the hygiene hypothesis. Scand J Immunol 2006; 64:125–136 [View Article] [PubMed]
     [Google Scholar]
  39. Jakobsson HE, Rodríguez-Piñeiro AM, Schütte A, Ermund A, Boysen P et al. The composition of the gut microbiota shapes the colon mucus barrier. EMBO Rep 2015; 16:164–177 [View Article] [PubMed]
     [Google Scholar]
  40. Rosshart SP, Vassallo BG, Angeletti D, Hutchinson DS, Morgan AP et al. Wild mouse gut microbiota promotes host fitness and improves disease resistance. Cell 2017; 171:1015–1028 [View Article] [PubMed]
     [Google Scholar]
  41. Rosshart SP, Herz J, Vassallo BG, Hunter A, Wall MK et al. Laboratory mice born to wild mice have natural microbiota and model human immune responses. Science 2019; 365:eaaw4361 [View Article] [PubMed]
     [Google Scholar]
  42. Rowe FP, Bradfield A, Quy RJ, Swinney T. Relationship between eye lens weight and age in the wild house mouse (Mus musculus). THE Journal of Applied Ecology 1985; 22:55 [View Article]
     [Google Scholar]
  43. Roble GS, Gillespie V, Lipman NS. Infectious disease survey of Mus musculus from pet stores in New York City. J Am Assoc Lab Anim Sci 2012; 51:37–41 [PubMed]
     [Google Scholar]
  44. Beura LK, Hamilton SE, Bi K, Schenkel JM, Odumade OA et al. Normalizing the environment recapitulates adult human immune traits in laboratory mice. Nature 2016; 532:512–516 [View Article] [PubMed]
     [Google Scholar]
  45. Fiege JK, Block KE, Pierson MJ, Nanda H, Shepherd FK et al. Mice with diverse microbial exposure histories as a model for preclinical vaccine testing. Cell Host Microbe 2021; 29:1815–1827 [View Article] [PubMed]
     [Google Scholar]
  46. Huggins MA, Sjaastad FV, Pierson M, Kucaba TA, Swanson W et al. Microbial exposure enhances immunity to pathogens recognized by TLR2 but increases susceptibility to cytokine storm through TLR4 sensitization. Cell Rep 2019; 28:1729–1743 [View Article] [PubMed]
     [Google Scholar]
  47. Pierson M, Merley A, Hamilton SE. Generating mice with diverse microbial experience. Curr Protoc 2021; 1:e53 [View Article] [PubMed]
     [Google Scholar]
  48. Sjaastad FV, Kucaba TA, Dileepan T, Swanson W, Dail C et al. Polymicrobial sepsis impairs antigen-specific memory CD4 T cell-mediated immunity. Front Immunol 2020; 11:1786 [View Article] [PubMed]
     [Google Scholar]
  49. Beura LK, Wijeyesinghe S, Thompson EA, Macchietto MG, Rosato PC et al. T cells in nonlymphoid tissues give rise to lymph-node-resident memory T cells. Immunity 2018; 48:327–338 [View Article] [PubMed]
     [Google Scholar]
  50. Choi YJ, Kim S, Choi Y, Nielsen TB, Yan J et al. SERPINB1-mediated checkpoint of inflammatory caspase activation. Nat Immunol 2019; 20:276–287 [View Article] [PubMed]
     [Google Scholar]
  51. Takeda AJ, Maher TJ, Zhang Y, Lanahan SM, Bucklin ML et al. Human PI3Kγ deficiency and its microbiota-dependent mouse model reveal immunodeficiency and tissue immunopathology. Nat Commun 2019; 10:4364 [View Article] [PubMed]
     [Google Scholar]
  52. Wijeyesinghe S, Beura LK, Pierson MJ, Stolley JM, Adam OA et al. Expansible residence decentralizes immune homeostasis. Nature 2021; 592:457–462 [View Article] [PubMed]
     [Google Scholar]
  53. Beura LK, Fares-Frederickson NJ, Steinert EM, Scott MC, Thompson EA et al. CD4+ resident memory T cells dominate immunosurveillance and orchestrate local recall responses. J Exp Med 2019; 216:1214–1229 [View Article] [PubMed]
     [Google Scholar]
  54. Kash JC, Tumpey TM, Proll SC, Carter V, Perwitasari O et al. Genomic analysis of increased host immune and cell death responses induced by 1918 influenza virus. Nature 2006; 443:578–581 [View Article] [PubMed]
     [Google Scholar]
  55. Kobasa D, Jones SM, Shinya K, Kash JC, Copps J et al. Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus. Nature 2007; 445:319–323 [View Article] [PubMed]
     [Google Scholar]
  56. Tisoncik JR, Korth MJ, Simmons CP, Farrar J, Martin TR et al. Into the eye of the cytokine storm. Microbiol Mol Biol Rev 2012; 76:16–32 [View Article] [PubMed]
     [Google Scholar]
  57. Beyersdorf N, Gaupp S, Balbach K, Schmidt J, Toyka KV et al. Selective targeting of regulatory T cells with CD28 superagonists allows effective therapy of experimental autoimmune encephalomyelitis. J Exp Med 2005; 202:445–455 [View Article] [PubMed]
     [Google Scholar]
  58. Tacke M, Hanke G, Hanke T, Hünig T. CD28-mediated induction of proliferation in resting T cells in vitro and in vivo without engagement of the T cell receptor: evidence for functionally distinct forms of CD28. Eur J Immunol 1997; 27:239–247 [View Article] [PubMed]
     [Google Scholar]
  59. Beutler B, Milsark IW, Cerami AC. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science 1985; 229:869–871 [View Article] [PubMed]
     [Google Scholar]
  60. Leung JM, Budischak SA, Chung The H, Hansen C, Bowcutt R et al. Rapid environmental effects on gut nematode susceptibility in rewilded mice. PLoS Biol 2018; 16:e2004108 [View Article] [PubMed]
     [Google Scholar]
  61. Yeung F, Chen YH, Lin JD, Leung JM, McCauley C et al. Altered immunity of laboratory mice in the natural environment is associated with fungal colonization. Cell Host Microbe 2020; 27:809–822 [View Article] [PubMed]
     [Google Scholar]
  62. Lin JD, Devlin JC, Yeung F, McCauley C, Leung JM et al. Rewilding Nod2 and Atg16l1 mutant mice uncovers genetic and environmental contributions to microbial responses and immune cell composition. Cell Host Microbe 2020; 27:830–840 [View Article] [PubMed]
     [Google Scholar]
  63. Arnesen H, Knutsen LE, Hognestad BW, Johansen GM, Bemark M et al. A model system for feralizing laboratory mice in large farmyard-like pens. Front Microbiol 2020; 11:615661 [View Article] [PubMed]
     [Google Scholar]
  64. Lindner C, Thomsen I, Wahl B, Ugur M, Sethi MK et al. Diversification of memory B cells drives the continuous adaptation of secretory antibodies to gut microbiota. Nat Immunol 2015; 16:880–888 [View Article] [PubMed]
     [Google Scholar]
  65. Reese TA, Bi K, Kambal A, Filali-Mouhim A, Beura LK et al. Sequential infection with common pathogens promotes human-like immune gene expression and altered vaccine response. Cell Host Microbe 2016; 19:713–719 [View Article] [PubMed]
     [Google Scholar]
  66. Chiu CY, Greninger AL, Kanada K, Kwok T, Fischer KF et al. Identification of cardioviruses related to Theiler’s murine encephalomyelitis virus in human infections. Proc Natl Acad Sci U S A 2008; 105:14124–14129 [View Article] [PubMed]
     [Google Scholar]
  67. Wylie TN, Wylie KM, Herter BN, Storch GA. Enhanced virome sequencing using targeted sequence capture. Genome Res 2015; 25:1910–1920 [View Article] [PubMed]
     [Google Scholar]
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Embracing the heterogeneity of natural viruses in mouse studies
J. Gen. Virol. 103, 001758 (2022); https://doi.org/10.1099/jgv.0.001758
/content/journal/jgv/10.1099/jgv.0.001758
/content/journal/jgv/10.1099/jgv.0.001758
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