Skip to main content

Advertisement

Log in

Alternating Host Cell Tropism Shapes the Persistence, Evolution and Coexistence of Epstein–Barr Virus Infections in Human

  • Original Article
  • Published:
Bulletin of Mathematical Biology Aims and scope Submit manuscript

Abstract

Epstein–Barr virus (EBV) infects and can persist in a majority of people worldwide. Within an infected host, EBV targets two major cell types, B cells and epithelial cells, and viruses emerging from one cell type preferentially infect the other. We use mathematical models to understand why EBV infects epithelial cells when B cells serve as a stable refuge for the virus and how switching between infecting each cell type affects virus persistence and shedding. We propose a mathematical model to describe the regulation of EBV infection within a host. This model is used to study the effects of parameter values on optimal viral strategies for transmission, persistence, and intrahost competition. Most often, the optimal strategy to maximize transmission is for viruses to infect epithelial cells, but the optimal strategy for maximizing intrahost competition is for viruses to mainly infect B cells. Applying the results of the within-host model, we derive a model of EBV dynamics in a homogeneous population of hosts that includes superinfection. We use this model to study the conditions necessary for invasion and coexistence of various viral strategies at the population level. When the importance of intrahost competition is weak, we show that coexistence of different strategies is possible.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Adler, F. R., & Mosquera, J. (2000). Is space necessary? Interference competition and limits to biodiversity. Ecology, 81(11), 3226–3232.

    Article  Google Scholar 

  • Andiman, W. A. (2006). Epidemiology of primary Epstein–Barr virus infection and infectious mononucleosis. In A. Tselis & H. B. Jenson (Eds.), Epstein–Barr virus (Vol. 1, 1st ed., pp. 39–57). New York: Taylor & Francis.

    Chapter  Google Scholar 

  • Borza, C. M., & Hutt-Fletcher, L. M. (2002). Alternate replication in B cells and epithelial cells switches tropism of Epstein–Barr virus. Nat. Med., 8(6), 594–599.

    Article  Google Scholar 

  • Borza, C. M., Morgan, A. J., Turk, S. M., & Hutt-Fletcher, L. M. (2004). Use of gHgL for attachment of Epstein–Barr virus to epithelial cells compromises infection. J. Virol., 7(10), 5007–5014.

    Article  Google Scholar 

  • Bremermann, H. J., & Thieme, H. R. (1989). A competitive exclusion principle for pathogen virulence. J. Math. Biol., 27(2), 179–190.

    Article  MATH  MathSciNet  Google Scholar 

  • Castiglione, F., Duca, K., Jarrah, A., Laubenbacher, R., Hochberg, D., & Thorley-Lawson, D. A. (2007). Simulating Epstein–Barr virus infection with C-ImmSim. Bioinformatics, 23(11), 1371–1377.

    Article  Google Scholar 

  • Davenport, M., Fazou, C., McMichael, A. J., & Callan, M. F. C. (2002). Clonal selection, clonal senescence, and clonal succession: the evolution of the T cell response to infection with a persistent virus. J. Immunol., 168(7), 3309–3317.

    Google Scholar 

  • Haan, K. M., Kwok, W. W., Longnecker, R., & Speck, P. (2000). Epstein–Barr virus entry utilizing HLA-DP or HLA-DQ as a coreceptor. J. Virol., 74(5), 2451–2454.

    Article  Google Scholar 

  • Heffernan, J. M., Smith, R. J., & Wahl, L. M. (2005). Perspectives on the basic reproductive ratio. J. R. Soc. Interface, 2(4), 281–293.

    Article  Google Scholar 

  • Hislop, A. D., Taylor, G. S., Sauce, D., & Rickinson, A. B. (2007). Cellular responses to viral infection in humans: lessons from Epstein–Barr virus. Annu. Rev. Immunol., 25(1), 587–617.

    Article  Google Scholar 

  • Hutt-Fletcher, L. M. (2005). EBV entry and epithelial infection. In E. S. Robertson (Ed.), Epstein–Barr virus (Vol. 1, 1st ed., pp. 359–378). Norfolk: Caister Academic Press.

    Google Scholar 

  • Hutt-Fletcher, L. M. (2007). Epstein–Barr virus entry. J. Virol., 81(15), 7825–7832.

    Article  Google Scholar 

  • Jiang, R., Scott, R. S., & Hutt-Fletcher, L. M. (2006). Epstein–Barr virus shed in saliva is high in B-cell-tropic gp42. J. Virol., 80(14), 7281–7283.

    Article  Google Scholar 

  • Jones, L., & Perelson, A. (2005). Opportunistic infection as a cause of transient viremia in chronically infected HIV patients under treatment with HAART. Bull. Math. Biol., 67(6), 1227–1251.

    Article  MathSciNet  Google Scholar 

  • Macallan, D. C., Wallace, D. L., Zhang, Y., Ghattas, H., Asquith, B., Lara, C., Worth, A., Panayiotakopoulos, G., Griffin, G. E., Tough, D. F., & Beverley, P. C. (2005). B-cell kinetics in humans: rapid turnover of peripheral blood memory cells. Blood, 105(9), 3633–3640.

    Article  Google Scholar 

  • Mocarski, E. S., Shenk, T., & Pass, R. F. (2007). Cytomegaloviruses. In D. M. Knipe & P. M. Howley (Eds.), Field’s virol (Vol. 2, 5th ed., pp. 2701–2772). Philadelphia: Williams & Wilkins.

    Google Scholar 

  • Mosquera, J., & Adler, F. R. (1998). Evolution of virulence: a unified framework for coinfection and superinfection. J. Theor. Biol., 195(3), 293–313.

    Article  Google Scholar 

  • Rickinson, A., & Kieff, E. (2001). Epstein-Barr Virus. In D. M. Knipe & P. M. Howley (Eds.), Field’s virol (Vol. 2, 4th ed., pp. 2575–2627). Philadelphia: Williams & Wilkins.

    Google Scholar 

  • Robertson, E. S. (Ed.) (2005). Epstein-Barr virus (Vol. 1, 1st ed.). Norfolk: Caister Academic Press.

    Google Scholar 

  • Shapiro, M., Duca, K. A., Lee, K., Delgado-Eckert, E., Hawlins, J., Jarrah, A. S., Laubenbacher, R., Laubenbacher, R., Polys, N. F., Hadinoto, V., & Thorley-Lawson, D. A. (2008). A virtual look at Epstein–Barr virus infection: Simulation mechanism. J. Theor. Biol., 252(4), 633–648.

    Article  Google Scholar 

  • Sitki-Green, D., Covington, M., & Raab-Traubb, N. (2003). Compartmentalization and transmission of multiple Epstein–Barr virus strains in asymptomatic carriers. J. Virol., 77(3), 1840–1847.

    Article  Google Scholar 

  • Sixbey, J. W., & Yao, Q. Y. (1992). Immunoglobulin A-induced shift of Epstein–Barr virus tissue tropism. Science, 255(5051), 1578–1580.

    Article  Google Scholar 

  • Thorley-Lawson, D. A. (2005). EBV persistence and latent infection in vivo. In E. S. Robertson (Ed.), Epstein–Barr virus (Vol. 1, 1st ed., pp. 309–349). Norfolk: Caister Academic Press.

    Google Scholar 

  • Turk, S. M., Jiang, R., Chesnokova, L. S., & Hutt-Fletcher, L. M. (2006). Antibodies to gp350/220 enhance the ability of Epstein-Barr virus to infect epithelial cells. J. Virol., 80(19), 9628–9633.

    Article  Google Scholar 

  • van den Driessche, P., & Watmough, J. (2002). Reproduction numbers and sub-threshold endemic equilibria for compartmental models of disease transmission. Math. Biosci., 180(1–2), 29–48.

    MATH  MathSciNet  Google Scholar 

  • Wang, G., Krueger, G. R. F., & Buje, L. M. (2003). Mathematical model to simulate the cellular dynamics of infection with human herpesvirus-6 in EBV-negative infectious mononucleosis. J. Med. Virol., 71(4), 569–577.

    Article  Google Scholar 

  • Wodarz, D., Sierro, S., & Klenerman, P. (2007). Dynamics of killer T cell inflation in viral infections. J. R. Soc. Interface, 4(14), 533–543.

    Article  Google Scholar 

  • Yamanishi, K., Mori, Y., & Pellett, P. E. (2007). Human herpesviruses 6 and 7. In D. M. Knipe & P. M. Howley (Eds.), Field’s virol (Vol. 2, 5th ed., pp. 2701–2772). Philadelphia: Williams & Wilkins.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Giao T. Huynh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huynh, G.T., Adler, F.R. Alternating Host Cell Tropism Shapes the Persistence, Evolution and Coexistence of Epstein–Barr Virus Infections in Human. Bull Math Biol 73, 1754–1773 (2011). https://doi.org/10.1007/s11538-010-9590-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11538-010-9590-8

Keywords

Navigation