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Impact of CMV upon immune aging: facts and fiction

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Abstract

Aging is accompanied by significant defects in immunity and compromised responses to new, previously unencountered microbial pathogens. Most humans carry several persistent or latent viruses as they age, interacting with the host immune systems for years. In that context maybe the most studied persistent virus is Cytomegalovirus, infamous for its ability to recruit very large T cell responses which increase with age and to simultaneously evade elimination by the immune system. Here we will address how lifelong CMV infection and the immunological burden of its control might affect immune reactivity and health of the host over time.

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References

  1. Brodin P, Jojic V, Gao T et al (2015) Variation in the human immune system is largely driven by non-heritable influences. Cell 160:37–47. https://doi.org/10.1016/j.cell.2014.12.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bate SL, Dollard SC, Cannon MJ (2010) Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988–2004. Clin Infect Dis 50:1439–1447. https://doi.org/10.1086/652438

    Article  PubMed  Google Scholar 

  3. Aiello AE, Chiu YL, Frasca D (2017) How does cytomegalovirus factor into diseases of aging and vaccine responses, and by what mechanisms? GeroScience 39:261–271. https://doi.org/10.1007/s11357-017-9983-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Barton ES, White DW, Cathelyn JS et al (2007) Herpesvirus latency confers symbiotic protection from bacterial infection. Nature 447:326–329. https://doi.org/10.1038/nature05762

    Article  CAS  PubMed  Google Scholar 

  5. Furman D, Jojic V, Sharma S et al (2015) Cytomegalovirus infection enhances the immune response to influenza. Sci Transl Med. https://doi.org/10.1126/scitranslmed.aaa2293

    Article  PubMed  PubMed Central  Google Scholar 

  6. Smithey MJ, Venturi V, Davenport MP et al (2018) Lifelong CMV infection improves immune defense in old mice by broadening the mobilized TCR repertoire against third-party infection. Proc Natl Acad Sci. https://doi.org/10.1073/pnas.1719451115

    Article  PubMed  Google Scholar 

  7. Holtappels R, Pahl-Seibert M-F, Thomas D, Reddehase MJ (2000) Enrichment of immediate-early 1 (m123/pp89) peptide-specific CD8 T cells in a pulmonary CD62Llo memory-effector cell pool during latent murine cytomegalovirus infection of the lungs. J Virol 74:11495–11503. https://doi.org/10.1128/jvi.74.24.11495-11503.2000

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Karrer U, Sierro S, Wagner M et al (2003) Memory inflation: continuous accumulation of antiviral CD8 + T cells over time. J Immunol. https://doi.org/10.4049/jimmunol.170.4.2022

    Article  PubMed  Google Scholar 

  9. Komatsu H, Sierro S, Cuero VA, Klenerman P (2003) Population analysis of antiviral T cell responses using MHC class I-peptide tetramers. Clin Exp Immunol 134:9–12

    Article  CAS  Google Scholar 

  10. Morabito KM, Ruckwardt TJ, Bar-Haim E et al (2018) Memory inflation drives tissue-resident memory CD8 + T cell maintenance in the lung after intranasal vaccination with murine cytomegalovirus. Front Immunol 9:1861. https://doi.org/10.3389/fimmu.2018.01861

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Smith CJ, Turula H, Snyder CM (2014) Systemic hematogenous maintenance of memory inflation by MCMV infection. PLoS Pathog 10:e1004233. https://doi.org/10.1371/journal.ppat.1004233

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Munks M, Cho K, Pinto A et al (2006) Four distinct patterns of memory CD8 T cell responses to chronic murine cytomegalovirus infection. J Immunol 177:450–458. https://doi.org/10.4049/jimmunol.177.1.450

    Article  CAS  PubMed  Google Scholar 

  13. Sylwester AW, Mitchell BL, Edgar JB et al (2005) Broadly targeted human cytomegalovirus-specific CD4+ and CD8+ T cells dominate the memory compartments of exposed subjects. J Exp Med 202:673–685. https://doi.org/10.1084/jem.20050882

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Klenerman P, Oxenius A (2016) T cell responses to cytomegalovirus. Nat Rev Immunol 16:367

    Article  CAS  Google Scholar 

  15. Wertheimer AM, Bennett MS, Park B et al (2014) Aging and cytomegalovirus infection differentially and jointly affect distinct circulating T cell subsets in humans. J Immunol 192:2143–2155. https://doi.org/10.4049/jimmunol.1301721

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Polic B, Hengel H, Krmpotic A et al (1998) Hierarchical and redundant lymphocyte subset control precludes cytomegalovirus replication during latent infection. J Exp Med 188:1047–1054. https://doi.org/10.1084/jem.188.6.1047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Reddehase MJ, Balthesen M, Rapp M et al (1994) The conditions of primary infection define the load of latent viral genome in organs and the risk of recurrent cytomegalovirus disease. J Exp Med 179:185–193. https://doi.org/10.1084/jem.179.1.185

    Article  CAS  PubMed  Google Scholar 

  18. Reddehase MJ, Podlech J, Grzimek NKA (2002) Mouse models of cytomegalovirus latency: overview. J Clin Virol 25(Suppl 2):S23–S36

    Article  CAS  Google Scholar 

  19. Gordon CL, Miron M, Thome JJC et al (2017) Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection. J Exp Med. https://doi.org/10.1084/jem.20160758

    Article  PubMed  PubMed Central  Google Scholar 

  20. Goodrum F (2016) Human cytomegalovirus latency: approaching the gordian knot. Annu Rev Virol 3:333–357. https://doi.org/10.1146/annurev-virology-110615-042422

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Mendelson M, Monard S, Sissons P, Sinclair J (1996) Detection of endogenous human cytomegalovirus in CD34 + bone marrow progenitors. J Gen Virol 77:3099–3102. https://doi.org/10.1099/0022-1317-77-12-3099

    Article  CAS  PubMed  Google Scholar 

  22. Hahn G, Jores R, Mocarski ES (2002) Cytomegalovirus remains latent in a common precursor of dendritic and myeloid cells. Proc Natl Acad Sci 95:3937–3942. https://doi.org/10.1073/pnas.95.7.3937

    Article  Google Scholar 

  23. von Laer D, Meyer-Koenig U, Serr A et al (1995) Detection of cytomegalovirus DNA in CD34 + cells from blood and bone marrow. Blood 86:4086–4090

    Article  Google Scholar 

  24. Soderberg-Naucler C, Nelson JA, Allan-Yorke J et al (2002) Reactivation of latent human cytomegalovirus in CD14+ monocytes is differentiation dependent. J Virol 75:7543–7554. https://doi.org/10.1128/jvi.75.16.7543-7554.2001

    Article  Google Scholar 

  25. Jarvis MA, Nelson JA (2007) Human cytomegalovirus tropism for endothelial cells: not all endothelial cells are created equal. J Virol 81:2095–2101. https://doi.org/10.1128/JVI.01422-06

    Article  CAS  PubMed  Google Scholar 

  26. Seckert CK, Kuhnapfel B, Krause C et al (2009) Liver sinusoidal endothelial cells are a site of murine cytomegalovirus latency and reactivation. J Virol 83:8869–8884. https://doi.org/10.1128/jvi.00870-09

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Reddehase MJ, Lemmermann NAW (2019) Cellular reservoirs of latent cytomegaloviruses. Med Microbiol Immunol. https://doi.org/10.1007/s00430-019-00592-y

    Article  PubMed  PubMed Central  Google Scholar 

  28. Thom JT, Oxenius A (2016) Tissue-resident memory T cells in cytomegalovirus infection. Curr Opin Virol 16:63–69. https://doi.org/10.1016/j.coviro.2016.01.014

    Article  CAS  PubMed  Google Scholar 

  29. Turner DL, Bickham KL, Thome JJ et al (2014) Lung niches for the generation and maintenance of tissue-resident memory T cells. Mucosal Immunol 7:501–510. https://doi.org/10.1038/mi.2013.67

    Article  CAS  PubMed  Google Scholar 

  30. van Aalderen MC, Remmerswaal EBM, ten Berge IJM, van Lier RAW (2014) Blood and beyond: properties of circulating and tissue-resident human virus-specific αβ CD8+ T cells. Eur J Immunol 44:934–944. https://doi.org/10.1002/eji.201344269

    Article  CAS  PubMed  Google Scholar 

  31. Thom JT, Weber TC, Walton M, Torti N (2015) The salivary gland acts as a sink for tissue-resident memory CD8+ T cells, facilitating protection from local cytomegalovirus infection. Cell Rep. https://doi.org/10.1016/j.celrep.2015.09.082

    Article  PubMed  Google Scholar 

  32. Farrell HE, Lawler C, Tan CSE et al (2016) Murine cytomegalovirus exploits olfaction to enter new hosts. MBio 7:e00251-16. https://doi.org/10.1128/mBio.00251-16

    Article  PubMed  PubMed Central  Google Scholar 

  33. Arens R, Wang P, Sidney J et al (2008) Cutting edge: murine cytomegalovirus induces a polyfunctional CD4 T cell response. J Immunol 180:6472–6476

    Article  CAS  Google Scholar 

  34. Popovic B, Golemac M, Podlech J et al (2017) IL-33/ST2 pathway drives regulatory T cell dependent suppression of liver damage upon cytomegalovirus infection. PLoS Pathog 13:e1006345. https://doi.org/10.1371/journal.ppat.1006345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Munks MW, Gold MC, Zajac AL et al (2006) Genome-wide analysis reveals a highly diverse CD8 T cell response to murine cytomegalovirus. J Immunol 176:3760–3766. https://doi.org/10.4049/JIMMUNOL.176.6.3760

    Article  CAS  PubMed  Google Scholar 

  36. O’Hara GA, Welten SPM, Klenerman P, Arens R (2012) Memory T cell inflation: understanding cause and effect. Trends Immunol 33:84–90. https://doi.org/10.1016/j.it.2011.11.005

    Article  CAS  PubMed  Google Scholar 

  37. Derhovanessian E, Larbi A, Pawelec G (2009) Biomarkers of human immunosenescence: impact of cytomegalovirus infection. Curr Opin Immunol 21:440–445. https://doi.org/10.1016/j.coi.2009.05.012

    Article  CAS  PubMed  Google Scholar 

  38. Jackson SE, Mason GM, Okecha G et al (2014) Diverse specificities, phenotypes, and antiviral activities of cytomegalovirus-specific CD8+ T cells. J Virol 88:10894–10908. https://doi.org/10.1128/JVI.01477-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Lang A, Brien JD, Nikolich-Zugich J (2009) Inflation and long-term maintenance of CD8 T cells responding to a latent herpesvirus depend upon establishment of latency and presence of viral antigens. J Immunol 183:8077–8087. https://doi.org/10.4049/jimmunol.0801117

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Cicin-Sain L, Sylwester AW, Hagen SI et al (2011) Cytomegalovirus-specific T cell immunity is maintained in immunosenescent rhesus macaques. J Immunol 187:1722–1732. https://doi.org/10.4049/jimmunol.1100560

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Vieira Braga FA, Hertoghs KML, van Lier RAW, van Gisbergen KPJM (2015) Molecular characterization of HCMV-specific immune responses: parallels between CD8+ T cells, CD4+ T cells, and NK cells. Eur J Immunol 45:2433–2445. https://doi.org/10.1002/eji.201545495

    Article  CAS  PubMed  Google Scholar 

  42. Nikolich-Zugich J (2008) Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections. Nat Rev Immunol 8:512–522. https://doi.org/10.1038/nri2318

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Slobedman B, Mocarski ES (1999) Quantitative analysis of latent human cytomegalovirus. J Virol 73:4806–4812

    Article  CAS  Google Scholar 

  44. Ljungman P, Hakki M, Boeckh M (2011) Cytomegalovirus in hematopoietic stem cell transplant recipients. Hematol Oncol Clin N Am 25:151–169. https://doi.org/10.1016/J.HOC.2010.11.011

    Article  Google Scholar 

  45. Kuo CP, Wu CL, Ho HT et al (2008) Detection of cytomegalovirus reactivation in cancer patients receiving chemotherapy. Clin Microbiol Infect 14:221–227. https://doi.org/10.1111/j.1469-0691.2007.01895.x

    Article  CAS  PubMed  Google Scholar 

  46. Kurz SK, Reddehase MJ (1999) Patchwork pattern of transcriptional reactivation in the lungs indicates sequential checkpoints in the transition from murine cytomegalovirus latency to recurrence. J Virol 73:8612–8622

    Article  CAS  Google Scholar 

  47. Simon CO, Holtappels R, Tervo HM, Böhm V et al (2006) CD8 T cells control cytomegalovirus latency by epitope-specific sensing of transcriptional reactivation. J Virol 80:10436–10456. https://doi.org/10.1128/jvi.01248-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Seckert CK, Simon CO, Grießl M et al (2012) Viral latency drives ‘memory inflation’: a unifying hypothesis linking two hallmarks of cytomegalovirus infection. Med Microbiol Immunol 201:551–566. https://doi.org/10.1007/s00430-012-0273-y

    Article  PubMed  Google Scholar 

  49. Wertheim-van Dillen PME, Yong S-L, ten Berge IJM et al (2014) The size and phenotype of virus-specific T cell populations is determined by repetitive antigenic stimulation and environmental cytokines. J Immunol 172:6107–6114. https://doi.org/10.4049/jimmunol.172.10.6107

    Article  Google Scholar 

  50. Souquette A, Frere J, Smithey M et al (2017) A constant companion: immune recognition and response to cytomegalovirus with aging and implications for immune fitness. GeroScience 39:293–303. https://doi.org/10.1007/s11357-017-9982-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Thimme R, Appay V, Koschella M et al (2005) Increased expression of the NK cell receptor KLRG1 by virus-specific CD8 T cells during persistent antigen stimulation. J Virol 79:12112–12116. https://doi.org/10.1128/JVI.79.18.12112-12116.2005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Nikolich-Žugich J (2018) The twilight of immunity: emerging concepts in aging of the immune system. Nat Immunol 19:10–19. https://doi.org/10.1038/s41590-017-0006-x

    Article  CAS  PubMed  Google Scholar 

  53. Springer KL, Weinberg A (2004) Cytomegalovirus infection in the era of HAART: fewer reactivations and more immunity. J Antimicrob Chemother 54:582–586. https://doi.org/10.1093/jac/dkh396

    Article  CAS  PubMed  Google Scholar 

  54. McGuinness BJ, Ferguson RM, Zhang Y et al (2002) Intra-abdominal bacterial infection reactivates latent pulmonary cytomegalovirus in immunocompetent mice. J Infect Dis 185:1395–1400. https://doi.org/10.1086/340508

    Article  PubMed  Google Scholar 

  55. Cook CH, Trgovcich J, Zimmerman PD et al (2006) Lipopolysaccharide, tumor necrosis factor alpha, or interleukin-1 triggers reactivation of latent cytomegalovirus in immunocompetent mice. J Virol 80:9151–9158. https://doi.org/10.1128/JVI.00216-06

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Simon CO, Seckert CK, Dreis D et al (2005) Role for tumor necrosis factor alpha in murine cytomegalovirus transcriptional reactivation in latently infected lungs. J Virol 79:326–340. https://doi.org/10.1128/JVI.79.1.326

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Forte E, Swaminathan S, Schroeder MW et al (2018) Tumor necrosis factor alpha induces reactivation of human cytomegalovirus independently of myeloid cell differentiation following posttranscriptional establishment of latency. MBio 9:1–15. https://doi.org/10.1128/mBio.01560-18

    Article  Google Scholar 

  58. Beura LK, Hamilton SE, Bi K et al (2016) Normalizing the environment recapitulates adult human immune traits in laboratory mice. Nature 532:512–516. https://doi.org/10.1038/nature17655

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Rector JL, Dowd JB, Loerbroks A et al (2014) Consistent associations between measures of psychological stress and CMV antibody levels in a large occupational sample. Brain Behav Immun 38:133–141. https://doi.org/10.1016/j.bbi.2014.01.012

    Article  PubMed  Google Scholar 

  60. Leng SX, Kamil J, Purdy JG et al (2017) Recent advances in CMV tropism, latency, and diagnosis during aging. GeroScience 39:251–259. https://doi.org/10.1007/s11357-017-9985-7

    Article  PubMed  PubMed Central  Google Scholar 

  61. Vescovini R, Fagnoni FF, Telera AR et al (2014) Naïve and memory CD8 T cell pool homeostasis in advanced aging: impact of age and of antigen-specific responses to cytomegalovirus. Age (Dordr) 36:625–640. https://doi.org/10.1007/s11357-013-9594-z

    Article  CAS  Google Scholar 

  62. Smithey MJ, Li G, Venturi V et al (2012) Lifelong persistent viral infection alters the naive T cell pool, impairing CD8 T cell immunity in late life. J Immunol 189:5356–5366. https://doi.org/10.4049/jimmunol.1201867

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Cicin-Sain L, Messaoudi I, Park B et al (2007) Dramatic increase in naive T cell turnover is linked to loss of naive T cells from old primates. Proc Natl Acad Sci USA 104:19960–19965. https://doi.org/10.1073/pnas.0705905104

    Article  PubMed  Google Scholar 

  64. Thompson HL, Smithey MJ, Surh CD, Nikolich-Žugich J (2017) Functional and homeostatic impact of age-related changes in lymph node stroma. Front Immunol 8:1–8. https://doi.org/10.3389/fimmu.2017.00706

    Article  CAS  Google Scholar 

  65. Nikolich-Zugich J, Li G, Uhrlaub JL et al (2012) Age-related changes in CD8 T cell homeostasis and immunity to infection. Semin Immunol 24:356–364. https://doi.org/10.1016/j.smim.2012.04.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Casrouge A, Beaudoing E, Dalle S et al (2000) Size Estimate of the αβ TCR Repertoire of Naive Mouse Splenocytes. J Immunol 164:5782–5787. https://doi.org/10.4049/jimmunol.164.11.578267

    Article  CAS  PubMed  Google Scholar 

  67. Qi Q, Liu Y, Cheng Y et al (2014) Diversity and clonal selection in the human T-cell repertoire. Proc Natl Acad Sci 111:13139–13144. https://doi.org/10.1073/pnas.1409155111

    Article  CAS  PubMed  Google Scholar 

  68. Weekes MP, Carmichael AJ, Wills MR et al (1999) Human CD28−CD8+ T cells contain greatly expanded functional virus-specific memory CTL clones. J Immunol 162:7569–7577. https://doi.org/10.4049/jimmunol.168.1.29

    Article  CAS  PubMed  Google Scholar 

  69. Gillespie GMA, Murphy M, Moss PAH et al (2002) Functional heterogeneity and high frequencies of cytomegalovirus-specific CD8+ T lymphocytes in healthy seropositive donors. J Virol 74:8140–8150. https://doi.org/10.1128/jvi.74.17.8140-8150.2000

    Article  Google Scholar 

  70. Khan N, Shariff N, Cobbold M et al (2019) Cytomegalovirus seropositivity drives the CD8 T cell repertoire toward greater clonality in healthy elderly individuals. J Immunol. https://doi.org/10.4049/jimmunol.169.4.1984

    Article  PubMed  PubMed Central  Google Scholar 

  71. Britanova OV, Putintseva EV, Shugay M et al (2019) Age-related decrease in TCR repertoire diversity measured with deep and normalized sequence profiling. J Immunol. https://doi.org/10.4049/jimmunol.1302064

    Article  Google Scholar 

  72. Robins HS, Campregher PV, Srivastava SK et al (2009) Comprehensive assessment of T-cell receptor β-chain diversity in αβ T cells. Blood 114:4099–4107. https://doi.org/10.1182/blood-2009-04-217604

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Thome JJC, Grinshpun B, Kumar BV et al (2016) Long-term maintenance of human naïve T cells through in situ homeostasis in lymphoid tissue sites. Sci Immunol 1:eaah6506. https://doi.org/10.1126/sciimmunol.aah6506

    Article  PubMed  PubMed Central  Google Scholar 

  74. Yager EJ, Ahmed M, Lanzer K et al (2008) Age-associated decline in T cell repertoire diversity leads to holes in the repertoire and impaired immunity to influenza virus. J Exp Med 205:711–723. https://doi.org/10.1084/jem.20071140

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Quinn KM, Zaloumis SG, Cukalac T et al (2016) Heightened self-reactivity associated with selective survival, but not expansion, of naïve virus-specific CD8+ T cells in aged mice. Proc Natl Acad Sci USA 113:1333–1338. https://doi.org/10.1073/pnas.1525167113

    Article  CAS  PubMed  Google Scholar 

  76. Rudd BD, Venturi V, Davenport MP, Nikolich-Zugich J (2011) Evolution of the antigen-specific CD8+ TCR repertoire across the life span: evidence for clonal homogenization of the old TCR repertoire. J Immunol 186:2056–2064. https://doi.org/10.4049/jimmunol.1003013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Pawelec G, Akbar A, Caruso C et al (2004) Is immunosenescence infectious? Trends Immunol 25:406–410. https://doi.org/10.1016/j.it.2004.05.006

    Article  CAS  PubMed  Google Scholar 

  78. Tu W, Rao S (2016) Mechanisms underlying T cell immunosenescence: aging and cytomegalovirus infection. Front Microbiol 7:1–12. https://doi.org/10.3389/fmicb.2016.02111

    Article  Google Scholar 

  79. Cicin-Sain L, Brien JD, Uhrlaub JL et al (2012) Cytomegalovirus infection impairs immune responses and accentuates T-cell pool changes observed in mice with aging. PLoS Pathog 8:e1002849. https://doi.org/10.1371/journal.ppat.1002849

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Mekker A, Tchang VS, Haeberli L et al (2012) Immune senescence: relative contributions of age and cytomegalovirus infection. PLoS Pathog. https://doi.org/10.1371/journal.ppat.1002850

    Article  PubMed  PubMed Central  Google Scholar 

  81. Marandu TF, Oduro JD, Borkner L et al (2015) Immune protection against virus challenge in aging mice is not affected by latent herpesviral infections. J Virol 89:11715–11717. https://doi.org/10.1128/JVI.01989-15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Hislop AD, Buckley CD, Alan B et al (2005) Tonsillar homing of Epstein–Barr virus—specific CD8+ T cells and the virus–host balance Find the latest version : Tonsillar homing of Epstein–Barr virus—specific CD8+ T cells and the virus-host balance. J Clin Investig 115:2546–2555. https://doi.org/10.1172/JCI24810.2546

    Article  CAS  PubMed  Google Scholar 

  83. Sierro S, Rothkopf R, Klenerman P (2005) Evolution of diverse antiviral CD8+ T cell populations after murine cytomegalovirus infection. Eur J Immunol 35:1113–1123. https://doi.org/10.1002/eji.200425534

    Article  CAS  PubMed  Google Scholar 

  84. Jackson SE, Sedikides GX, Okecha G et al (2019) Generation, maintenance and tissue distribution of T cell responses to human cytomegalovirus in lytic and latent infection. Med Microbiol Immunol. https://doi.org/10.1007/s00430-019-00598-6

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Supported by the USPS award AG048021 from the NIH/NIA.

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  1. Department of Immunobiology and the University of Arizona Center on Aging, University of Arizona College of Medicine-Tucson, Tucson, AZ, 85718, USA

    Mladen Jergović, Nico A. Contreras & Janko Nikolich-Žugich

  2. University of Arizona College of Medicine-Tucson, 1501 N Campbell Ave, P.O. Box 221245, Tucson, AZ, 85724, USA

    Janko Nikolich-Žugich

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Jergović, M., Contreras, N.A. & Nikolich-Žugich, J. Impact of CMV upon immune aging: facts and fiction. Med Microbiol Immunol 208, 263–269 (2019). https://doi.org/10.1007/s00430-019-00605-w

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