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Impact of intracellular delay, immune activation delay and nonlinear incidence on viral dynamics

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Abstract

This paper investigates a class of viral infection models with a nonlinear infection rate and two discrete delays, one of which represents an intracellular latent period for the contacted target cell with virus to begin producing virions, the other of which represents the time needed in cytotoxic T cells (CTLs) response before immune becomes effective after a novel pathogen invades. Since immune system is a complex network of cells and signals that have evolved to respond to the presence of pathogens, we further assume two situations for immune activation delay. When both delays are ignored, the global stability for the ordinary differential equations model are established. While both delays are included, the positivity and boundedness of all solutions of the delay differential equations model are proved. Utilizing Lyapunov functionals and LaSalle invariance principle, the global dynamical properties are also studied. In particular, stability switch is shown to occur as immune delay increasing by bifurcation theory. Our results exhibit that the intracellular delay does not affect the stability of equilibria. However, the immune activation delay is able to destabilize the interior equilibrium and brings periodic solutions. Numerical simulations are performed to verify the theoretical results and display the different impacts of two type delays in two cases. Those analysis give us some useful suggestions on new drugs to fight against viral infection such that it is effective for the drugs to prolong the latent period, and/or to reduce the activation delay of CTLs immune response and/or to inhibit infection.

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References

  1. Anderson R., May R.M.: The population dynamics of microparasites and their invertebrate hosts. Philo. T. Roy. Soc. B. 291, 451–524 (1981)

    Article  Google Scholar 

  2. Beretta E., Kuang Y.: Geometric stability switch criteria in delay differential systems with delay dependent parameters. SIAM J. Math. Anal. 33, 1144–1165 (2002)

    Article  MathSciNet  MATH  Google Scholar 

  3. Beretta, E., Carletti, M., Kirschner D.E., Marino, S.: Stability analysis of a mathematical model of the immune response with delays, In: Mathematics for life science and medicine, pp. 177–206 (2007)

  4. Buric N., Mudrinic M., Vasovic N.: Time delay in a basic model of the immune response. Chaos Solut. Fractals 12, 483–489 (2001)

    Article  MATH  Google Scholar 

  5. Canabarro A.A, Gleria I.M., Lyra M.L.: Periodic solutions and chaos in a non-linear model for the delayed celluar immune response. Phys. A 342, 483–489 (2004)

    Google Scholar 

  6. Culshaw R.V., Ruan S.: A delay-differential equation model of HIV infection of CD4+ T-cells. Math. Biosci. 165, 27–39 (2000)

    Article  MATH  Google Scholar 

  7. Ebert D., Zschokke-Rohringer C.D., Carius H.J.: Does effects and density-dependent regulation of two microparasites of Daphnia magna. Oecologia 122, 200–209 (2000)

    Article  Google Scholar 

  8. Fenton A., Lello J., Bonsall M. B.: Pathogen responses to host immunity: the impact of time delays and memory on the evolution of virulence. Proc. R. Soc. B. 273, 2083–2090 (2006)

    Article  Google Scholar 

  9. Gourley S.A., Kuang Y., Nagy D.: Dynamics of a delay differential model of hepatitis B virus infection. J. Biol. Dyn. 2, 140–153 (2008)

    Article  MathSciNet  MATH  Google Scholar 

  10. Herz V., Bonhoeffer S., Anderson R., May R.M., Nowak M.A.: Viral dynamics in vivo: limitations on estimations on intracellular delay and virus delay. Proc. Natl. Acad. Sci. USA 93, 7247–7251 (1996)

    Article  Google Scholar 

  11. Huang G., Takeuchi Y., Ma W.: Lyapunov functionals for delay differential equations model for viral infections. SIAM J. Appl. Math. 70, 2693–2708 (2010)

    Article  MathSciNet  MATH  Google Scholar 

  12. Kajiwara T., Sasaki T.: A note on the stability analysis of pathogen–immune interaction dynamics. Disc. Cont. Dyn. Sys. B. 4, 615–622 (2004)

    Article  MathSciNet  MATH  Google Scholar 

  13. Korobeinikov A.: Global properties of basic virus dynamics models. Bull. Math. Biol. 66, 879–883 (2004)

    Article  MathSciNet  Google Scholar 

  14. Korobeinikov A.: Global asymptotic properties of virus dynamics models with dose dependent parasite reproduction and virulence, and nonlinear incidence rate. Math. Med. Biol. 26, 225–239 (2009)

    Article  MathSciNet  MATH  Google Scholar 

  15. Korobeinikov A.: Stability of ecosystem: global properties of a general prey-predator model. Math. Med. Biol. 26, 309–321 (2009)

    Article  MathSciNet  MATH  Google Scholar 

  16. Korobeinikov A.: Global properties of infectious disease models with non-linear incidence. Bull. Math. Biol. 69, 1871–1886 (2007)

    Article  MathSciNet  MATH  Google Scholar 

  17. Kuang Y.: Delay Differential Equations with Applications in Population Dynamics. Academics Press, San Diego (1993)

    MATH  Google Scholar 

  18. Li, M.Y., Shu, H.: Multiple stable periodic oscillations in a mathematical model of CTL response to HTLV-1 infection. Bull. Math. Biol. doi:10.1007/sl1538-010-9591-7 (in press)

  19. Mittler J.E., Sulzer B., Neumann A.U., Perelson A.: Influence of delayed viral production on viral dynamics in HIV-1 infected patients. Math. Biosci. 152, 143–163 (1998)

    Article  MATH  Google Scholar 

  20. Nelson P., Murray J., Perelson A.: A model of HIV-1 pathogenesis that includes an intracellular delay. Math. Biosci. 163, 201–215 (2000)

    Article  MathSciNet  MATH  Google Scholar 

  21. Nelson P., Perelson A.: Mathematical analysis of delay differential equation models of HIV-1 infection. Math. Biosci. 179, 73–94 (2002)

    Article  MathSciNet  MATH  Google Scholar 

  22. Nowak M.A., Bangham C.R.M.: Population dynamics of immune responses to persistent virus. Science 272, 74–79 (1996)

    Article  Google Scholar 

  23. Nowak M.A., May R.M., Sigmund K.: Immune responses against multiple epitopes. J. Theoret. Biol. 175, 325–353 (1995)

    Article  Google Scholar 

  24. Pang H., Wang W., Wang K.: Global properties of virus dynamics with CTL immune response. J. Southw. China Normal Univ. 30, 797–799 (2005)

    Google Scholar 

  25. Perelson A., Kirschner D.E., De Boer R.: Dynamics of HIV infection of CD4+ T cell. Math. Biosci. 114, 81–125 (1993)

    Article  MATH  Google Scholar 

  26. Song X., Wang S., Zhou X.: Stability and Hopf bifurcation for a viral infection model with delayed non-lytic immune response. J. Appl. Math. Comput. 33, 251–265 (2010)

    Article  MathSciNet  MATH  Google Scholar 

  27. Tam J.: Delay effect in a model for virus replication. IMA J. Math. Appl. Med. Biol. 16, 29–37 (1999)

    Article  MATH  Google Scholar 

  28. Wang Y., Zhou Y., Wu J., Heffernan J.: Oscillatory viral dynamics in a delay HIV pathogenesis model. Math. Biosci. 219, 104–112 (2009)

    Article  MathSciNet  MATH  Google Scholar 

  29. Wang K., Wang W., Pang H., Liu X.: Complex dynamic behavior in a viral model with delay immune response. Phys. D. 226, 197–208 (2007)

    Article  MathSciNet  MATH  Google Scholar 

  30. Wodarz D.: Hepatitis C virus dynamics and pathology: the role of CTL and antibody responses. J. Gen. Virol. 84, 1743–1750 (2003)

    Article  Google Scholar 

  31. Xu R., Ma Z.: An HBV model with diffusion and time delay. J. Theoret. Biol. 257, 499–509 (2009)

    Article  Google Scholar 

  32. Zhu H., Zuo X.: Dynamics of an HIV-1 infection model with cell-mediated immune response and intracellular delay. Disc. Cont. Dyn. Sys. B. 12, 511–524 (2009)

    MATH  Google Scholar 

Download references

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Correspondence to Yasuhiro Takeuchi.

Additional information

This research is partially supported by the Grant-in-Aid Scientific Research (C) No. 22540122, Japan Society for Promotion of Science.

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Huang, G., Yokoi, H., Takeuchi, Y. et al. Impact of intracellular delay, immune activation delay and nonlinear incidence on viral dynamics. Japan J. Indust. Appl. Math. 28, 383–411 (2011). https://doi.org/10.1007/s13160-011-0045-x

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  • DOI: https://doi.org/10.1007/s13160-011-0045-x

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