1887

Abstract

Cytomegaloviruses (CMVs) use myeloid cells to move within their hosts. Murine CMV (MCMV) colonizes the salivary glands for long-term shedding, and reaches them via CD11c infected cells. A need to recruit patrolling monocytes for systemic spread has been proposed, based on poor salivary gland infection in fractalkine receptor (CX3CR1)-deficient mice. We found no significant CX3CR1 dependence of salivary gland infection. CCL2 and the viral m131/m129 chemokine homologue were also redundant for acute MCMV spread, arguing against a need for inflammation or infection to recruit additional monocytes to the entry site. M131/m129 promoted salivary gland infection, but only after the initial seeding of infected cells to this site. Our data support the idea that MCMV disseminates by infecting and mobilizing tissue-resident dendritic cells.

Funding
This study was supported by the:
  • Queensland Government
    • Principle Award Recipient: Philip G. Stevenson
  • Australian Research Council (AU) (Award DP190101851)
    • Principle Award Recipient: Philip G. Stevenson
  • National Health and Medical Research Council (Award 1122070, 1140169)
    • Principle Award Recipient: Philip G. Stevenson
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2019-10-14
2024-05-12
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References

  1. Sinclair J, Reeves M. The intimate relationship between human cytomegalovirus and the dendritic cell lineage. Front Microbiol 2014; 5:389 [View Article]
    [Google Scholar]
  2. Maciejewski JP, Bruening EE, Donahue RE, Mocarski ES, Young NS et al. Infection of hematopoietic progenitor cells by human cytomegalovirus. Blood 1992; 80:170–178
    [Google Scholar]
  3. Goodrum F, Jordan CT, Terhune SS, High K, Shenk T. Differential outcomes of human cytomegalovirus infection in primitive hematopoietic cell subpopulations. Blood 2004; 104:687–695 [View Article]
    [Google Scholar]
  4. Pergam SA, Xie H, Sandhu R, Pollack M, Smith J et al. Efficiency and risk factors for CMV transmission in seronegative hematopoietic stem cell recipients. Biol Blood Marrow Transplant 2012; 18:1391–1400 [View Article]
    [Google Scholar]
  5. Mendelson M, Monard S, Sissons P, Sinclair J. Detection of endogenous human cytomegalovirus in CD34+ bone marrow progenitors. J Gen Virol 1996; 77:3099–3102 [View Article]
    [Google Scholar]
  6. von Laer D, Meyer-Koenig U, Serr A, Finke J, Kanz L et al. Detection of cytomegalovirus DNA in CD34+ cells from blood and bone marrow. Blood 1995; 86:4086–4090
    [Google Scholar]
  7. Seckert CK, Renzaho A, Reddehase MJ, Grzimek NKA. Hematopoietic stem cell transplantation with latently infected donors does not transmit virus to immunocompromised recipients in the murine model of cytomegalovirus infection. Med Microbiol Immunol 2008; 197:251–259 [View Article]
    [Google Scholar]
  8. Farrell HE, Stevenson PG. Cytomegalovirus host entry and spread. J Gen Virol 2019; 100:545–553 [View Article]
    [Google Scholar]
  9. Farrell HE, Bruce K, Lawler C, Oliveira M, Cardin R et al. Murine cytomegalovirus spreads by dendritic cell recirculation. mBio 2017; 8:e01264–17 [View Article]
    [Google Scholar]
  10. Farrell HE, Lawler C, Tan CSE, MacDonald K, Bruce K et al. Murine cytomegalovirus exploits olfaction to enter new hosts. mBio 2016; 7:e00251–16 [View Article]
    [Google Scholar]
  11. E X, Meraner P, Lu P, Perreira JM, Aker AM et al. OR14I1 is a receptor for the human cytomegalovirus pentameric complex and defines viral epithelial cell tropism. Proc Natl Acad Sci USA 2019; 116:7043–7052 [View Article]
    [Google Scholar]
  12. Farrell HE, Bruce K, Ma J, Davis-Poynter N, Stevenson PG. Human cytomegalovirus US28 allows dendritic cell exit from lymph nodes. J Gen Virol 2018; 99:1509–1514 [View Article]
    [Google Scholar]
  13. Collins TM, Quirk MR, Jordan MC. Biphasic viremia and viral gene expression in leukocytes during acute cytomegalovirus infection of mice. J Virol 1994; 68:6305–6311
    [Google Scholar]
  14. Stoddart CA, Cardin RD, Boname JM, Manning WC, Abenes GB et al. Peripheral blood mononuclear phagocytes mediate dissemination of murine cytomegalovirus. J Virol 1994; 68:6243–6253
    [Google Scholar]
  15. Farrell HE, Bruce K, Lawler C, Stevenson PG. Murine cytomegalovirus spread depends on the infected myeloid cell type. J Virol 2019; 93: [View Article]
    [Google Scholar]
  16. Saederup N, Lin YC, Dairaghi DJ, Schall TJ, Mocarski ES. Cytomegalovirus-Encoded beta chemokine promotes monocyte-associated viremia in the host. Proc Natl Acad Sci USA 1999; 96:10881–10886 [View Article]
    [Google Scholar]
  17. Daley-Bauer LP, Roback LJ, Wynn GM, Mocarski ES. Cytomegalovirus hijacks CX3CR1hi patrolling monocytes as immune-privileged vehicles for dissemination in mice. Cell Host Microbe 2014; 15:351–362 [View Article]
    [Google Scholar]
  18. Sacher T, Podlech J, Mohr CA, Jordan S, Ruzsics Z et al. The major virus-producing cell type during murine cytomegalovirus infection, the hepatocyte, is not the source of virus dissemination in the host. Cell Host Microbe 2008; 3:263–272 [View Article]
    [Google Scholar]
  19. Tang Y, Harrington A, Yang X, Friesel RE, Liaw L. The contribution of the Tie2+ lineage to primitive and definitive hematopoietic cells. Genesis 2010; 48:563–567 [View Article]
    [Google Scholar]
  20. Ginhoux F, Jung S. Monocytes and macrophages: developmental pathways and tissue homeostasis. Nat Rev Immunol 2014; 14:392–404 [View Article]
    [Google Scholar]
  21. Farrell HE, Davis-Poynter N, Bruce K, Lawler C, Dolken L et al. Lymph node macrophages restrict murine cytomegalovirus dissemination. J Virol 2015; 89:7147–7158 [View Article]
    [Google Scholar]
  22. Farrell HE, Bruce K, Lawler C, Cardin RD, Davis-Poynter NJ et al. Type 1 interferons and NK cells limit murine cytomegalovirus escape from the lymph node subcapsular sinus. PLoS Pathog 2016; 12:e1006069 [View Article]
    [Google Scholar]
  23. Epelman S, Lavine KJ, Randolph GJ. Origin and functions of tissue macrophages. Immunity 2014; 41:21–35 [View Article]
    [Google Scholar]
  24. Jung S, Aliberti J, Graemmel P, Sunshine MJ, Kreutzberg GW et al. Analysis of fractalkine receptor CX(3)CR1 function by targeted deletion and green fluorescent protein reporter gene insertion. Mol Cell Biol 2000; 20:4106–4114 [View Article]
    [Google Scholar]
  25. Hanna RN, Carlin LM, Hubbeling HG, Nackiewicz D, Green AM et al. The transcription factor Nr4a1 (Nur77) controls bone marrow differentiation and the survival of Ly6C- monocytes. Nat Immunol 2011; 12:778–785 [View Article]
    [Google Scholar]
  26. Hanna RN, Shaked I, Hubbeling HG, Punt JA, Wu R et al. Nr4A1 (Nur77) deletion polarizes macrophages toward an inflammatory phenotype and increases atherosclerosis. Circ Res 2012; 110:416–427 [View Article]
    [Google Scholar]
  27. Landsman L, Bar-On L, Zernecke A, Kim KW, Krauthgamer R et al. Cx3Cr1 is required for monocyte homeostasis and atherogenesis by promoting cell survival. Blood 2009; 113:963–972 [View Article]
    [Google Scholar]
  28. Johnson LA, Jackson DG. The chemokine CX3CL1 promotes trafficking of dendritic cells through inflamed lymphatics. J Cell Sci 2013; 126:5259–5270 [View Article]
    [Google Scholar]
  29. Frank T, Niemann I, Reichel A, Stamminger T. Emerging roles of cytomegalovirus-encoded G protein-coupled receptors during lytic and latent infection. Med Microbiol Immunol 2019; 208:447–456 [View Article]
    [Google Scholar]
  30. Burg JS, Ingram JR, Venkatakrishnan AJ, Jude KM, Dukkipati A et al. Structural biology. Structural basis for chemokine recognition and activation of a viral G protein-coupled receptor. Science 2015; 347:1113–1117 [View Article]
    [Google Scholar]
  31. Scalzo AA, Yokoyama WM. Cmv1 and natural killer cell responses to murine cytomegalovirus infection. Curr Top Microbiol Immunol 2008; 321:101–122 [View Article]
    [Google Scholar]
  32. Corbett AJ, Coudert JD, Forbes CA, Scalzo AA. Functional consequences of natural sequence variation of murine cytomegalovirus m157 for Ly49 receptor specificity and NK cell activation. J Immunol 2011; 186:1713–1722 [View Article]
    [Google Scholar]
  33. McWhorter AR, Smith LM, Masters LL, Chan B, Shellam GR et al. Natural killer cell dependent within-host competition arises during multiple MCMV infection: consequences for viral transmission and evolution. PLoS Pathog 2013; 9:e1003111 [View Article]
    [Google Scholar]
  34. Geissmann F, Jung S, Littman DR. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity 2003; 19:71–82 [View Article]
    [Google Scholar]
  35. Noda S, Aguirre SA, Bitmansour A, Brown JM, Sparer TE et al. Cytomegalovirus MCK-2 controls mobilization and recruitment of myeloid progenitor cells to facilitate dissemination. Blood 2006; 107:30–38 [View Article]
    [Google Scholar]
  36. Fleming P, Davis-Poynter N, Degli-Esposti M, Densley E, Papadimitriou J et al. The murine cytomegalovirus chemokine homolog, m131/129, is a determinant of viral pathogenicity. J Virol 1999; 73:6800–6809
    [Google Scholar]
  37. Wagner FM, Brizic I, Prager A, Trsan T, Arapovic M et al. The viral chemokine MCK-2 of murine cytomegalovirus promotes infection as part of a gH/gL/MCK-2 complex. PLoS Pathog 2013; 9:e1003493 [View Article]
    [Google Scholar]
  38. Yunis J, Farrell HE, Bruce K, Lawler C, Wyer O et al. Murine cytomegalovirus glycoprotein O promotes epithelial cell infection in vivo . J Virol 2019; 93:e01378–18 [View Article]
    [Google Scholar]
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