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The structure of $ \omega $-limit sets of asymptotically non-autonomous discrete dynamical systems
Complete dynamical analysis for a nonlinear HTLV-I infection model with distributed delay, CTL response and immune impairment
1. | Department of Mathematics, Hubei Minzu University, Enshi, 445000, China |
2. | School of Information and Mathematics, Yangtze University, Jingzhou, 434023, China |
3. | Department of Mathematics, Southern Illinois University, Carbondale, IL 62901, United States |
It is well known that CTL (cytotoxic T lymphocyte) immune response could be broadly classified into lytic and nonlytic components, nonlinear functions can better reproduce saturated effects in the interaction processes between cell and viral populations, and distributed intracellular delay can realistically reflect the stochastic element in the delay effects. For these reasons, we develop an HTLV-I (Human T-cell leukemia virus type I) infection model with nonlinear lytic and nonlytic CTL immune responses, nonlinear incidence rate, distributed intracellular delay and immune impairment. Through conducting complete analysis, it is revealed that all these factors influence the concentration level of infected T-cells at the chronic-infection equilibrium, whereas intracellular distributed delay and nonlinear incidence rate may change the expression of the basic reproduction number $ \mathfrak{R}_0 $ in the context where the model proposed still preserves the threshold dynamics. Our analysis results obtained may improve several existing works by comparison. We also perform global sensitivity analysis for $ \mathfrak{R}_0 $ in order to explore the effective strategies of lowering the concentration level of infected T-cells.
References:
[1] |
E. Avila-Vales, N. Chan-Chí and G. García-Almeida,
Analysis of a viral infection model with immune impairment, intracellular delay and general non-linear incidence rate, Chaos Solitons Fractals, 69 (2014), 1-9.
doi: 10.1016/j.chaos.2014.08.009. |
[2] |
C. Bartholdy, J. P. Christensen, D. Wodarz and A. R. Thomsen,
Persistent virus infection despite chronic cytotoxic T-lymphocyte activation in gamma interferon-deficient mice infected with lymphocytic choriomeningitis virus, J. Virol., 74 (2000), 10304-10311.
|
[3] |
A. Carpentier, et al., Modes of human T cell leukemia virus type 1 transmission, replication
and persistence, Viruses, 7 (2015), 3603–3624. |
[4] |
P. H. Crowley and E. K. Martin,
Functional responses and interference within and between year classes of a dragonfly population, J. N. Am. Benthol. Soc., 8 (1989), 211-221.
|
[5] |
R. V. Culshaw, S. G. Ruan and G. Webb,
A mathematical model of cell-to-cell spread of HIV-1 that includes a time delay, J. Math. Biol., 46 (2003), 425-444.
doi: 10.1007/s00285-002-0191-5. |
[6] |
R. J. De Boer, Which of our modeling predictions are robust?, PLoS Comput. Biol., 8 (2012), e10002593, 5 pp.
doi: 10.1371/journal.pcbi.1002593. |
[7] |
D. Ebert, C. D. Zschokke-Rohringer and H. J. Carius,
Dose effects and density-dependent regulation of two microparasites of Daphnia magna, Oecologia, 122 (2000), 200-209.
|
[8] |
A. Gessain and O. Cassar, Epidemiological aspects and world distribution of HTLV-1 infection, Front. Microbiol., 3 (2012), e388. |
[9] |
H. Gómez-Acevedo and M. Y. Li,
Backward bifurcation in a model for HTLV-I infection of CD4$^+$T cells, Bull. Math. Biol., 67 (2005), 101-114.
doi: 10.1016/j.bulm.2004.06.004. |
[10] |
J. K. Hale and S. M. Verduyn Lunel, Introduction to Functional Differential Equations, Appl. Math. Sci. 99, Springer-Verlag, New York, 1993.
doi: 10.1007/978-1-4612-0873-0. |
[11] |
J. K. Hale and J. Kato,
Phase space for retarded equation with infinite delay, Funkcial. Ekvac., 21 (1978), 11-41.
|
[12] |
Y. Hino, S. Murakami and T. Naito, Functional-Differential Equations With Infinite Delay, Lecture Notes in Math., 1473. Springer-Verlag, Berlin, 1991.
doi: 10.1007/978-1-4612-0873-0. |
[13] |
D. D. Ho, A. U. Neumann, A. S. Perelson, W. Chen, J. M. Leonard and M. Markowitz,
Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection, Nature, 373 (1995), 123-126.
|
[14] |
S. Jacobson,
Immunopathogenesis of HTLV-I associated neurological disease, J. Infect. Dis., 186 (2002), 187-192.
|
[15] |
Y. Ji and L. Liu,
Global stability of a delayed viral infection model with nonlinear immune response and general incidence rate, Discrete Contin. Dyn. Syst. Ser. B, 21 (2016), 133-149.
doi: 10.3934/dcdsb.2016.21.133. |
[16] |
J. P. La Salle, The Stability of Dynamical Systems, Regional Conference Series in Applied Mathematics, SIAM, Philadelphia, 1976. |
[17] |
X. L. Lai and X. F. Zou,
Modeling HIV-1 virus dynamics with both virus-to-cell infection and cell-to-cell transmission, SIAM J. Math. Anal., 74 (2014), 898-917.
doi: 10.1137/130930145. |
[18] |
B. R. Levin, M. Lipsitch and S. Bonhoeffer,
Population biology, evolution, and infectious disease: Convergence and synthesis, Science, 283 (1999), 806-809.
doi: 10.1126/science.283.5403.806. |
[19] |
S. M. Li and Y. C. Zhou,
Backward bifurcation of an HTLV-I model with immune response, Discrete Contin. Dyn. Syst. Ser. B, 21 (2016), 863-881.
doi: 10.3934/dcdsb.2016.21.863. |
[20] |
M. Y. Li and H. Y. Shu,
Multiple stable periodic oscillations in a mathematical model of CTL response to HTLV-I infection, Bull. Math. Biol., 73 (2011), 1774-1793.
doi: 10.1007/s11538-010-9591-7. |
[21] |
M. Y. Li and H. Y. Shu,
Global dynamics of a mathematical model for HTLV-I infection of CD4$^+$ T cells with delayed CTL response, Nonlinear Anal. RWA, 13 (2012), 1080-1092.
doi: 10.1016/j.nonrwa.2011.02.026. |
[22] |
X. J. Lu, L. L. Hui, S. Q. Liu and J. Li,
A mathematical model of HTLV-I infection with two time delays, Math. Biosci. Eng., 12 (2015), 431-449.
doi: 10.3934/mbe.2015.12.431. |
[23] |
N. MacDonald, Time Lags in Biological Models, Lecture Notes in Biomathematics, 27. Spring-Verlag, Heidelberg, 1978.
doi: 10.1007/978-1-4612-0873-0. |
[24] |
S. Marino, I. B. Hogue, C. J. Ray and D. E. Kirschner,
A methodology for performing global uncertainty and sensitivity analysis in systems biology, J. Theoret. Biol., 254 (2008), 178-196.
doi: 10.1016/j.jtbi.2008.04.011. |
[25] |
J. E. Mittler, B. Sulzer ac, A. U. Neumann ade and A. S. Perelson a,
Influence of delayed viral production on viral dynamics in HIV-1 infected patients, Math. Biosci., 152 (1998), 143-163.
doi: 10.1016/S0025-5564(98)10027-5. |
[26] |
Y. Nakata, Y. Enatsu and Y. Muroya, Complete global dynamics of a delayed viral infection model with lytic and nonlytic effectors, SeMA J., (2012), 27–50. |
[27] |
M. A. Nowak and C. R. M. Bangham,
Population dynamics of immune responses to persistent viruses, Science, 272 (1996), 74-79.
doi: 10.1126/science.272.5258.74. |
[28] |
C. M. Rooney, C. Y. C. Ng, S. Loftin, C. A. Smith, C. Li, R. A. Krance, M. K. Brenner, H. E. Heslop, C. M. Rooney, M. K. Brenner, M. K. Brenner, R. A. Krance and H. E. Heslop,
Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation, Lancet, 345 (1995), 9-13.
doi: 10.1016/S0140-6736(95)91150-2. |
[29] |
H. Y. Shu, L. Wang and J. Watmough,
Global stability of a nonlinear viral infection model with infinitely distributed intracellular delays and CTL immune responses, SIAM J. Appl. Math., 73 (2013), 1280-1302.
doi: 10.1137/120896463. |
[30] |
R. P. Sigdel and C. C. McCluskey,
Global stability for an SEI model of infectious disease with immigration, Appl. Math. Comput., 243 (2014), 684-689.
doi: 10.1016/j.amc.2014.06.020. |
[31] |
N. I. Stilianakis and J. Seydel,
Modeling the T-cell dynamics and pathogenesis of HTLV-I infection, Bull. Math. Biol., 61 (1999), 935-947.
doi: 10.1006/bulm.1999.0117. |
[32] |
C. Vargas-De-León,
Global properties for a virus dynamics model with lytic and nonlytic immune responses and nonlinear immune attack rates, J. Biol. Syst., 22 (2014), 449-462.
doi: 10.1142/S021833901450017X. |
[33] |
J. L. Wang, M. Guo, X. N. Liu and Z. T. Zhao,
Threshold dynamics of HIV-1 virus model with cell-to-cell transmission, cell-mediated immune responses and distributed delay, Appl. Math. Comput., 291 (2016), 149-161.
doi: 10.1016/j.amc.2016.06.032. |
[34] |
K. F. Wang, W. D. Wang and X. N. Liu,
Global stability in a viral infection model with lytic and nonlytic immune responses, Comput. Math. Appl., 51 (2006), 1593-1610.
doi: 10.1016/j.camwa.2005.07.020. |
[35] |
S. L. Wang, X. Y. Song and Z. H. Ge,
Dynamics analysis of a delayed viral infection model with immune impairment, Appl. Math. Model., 35 (2011), 4877-4885.
doi: 10.1016/j.apm.2011.03.043. |
[36] |
Y. Wang, J. Liu and J. M. Heffernan,
Viral dynamics of an HTLV-I infection model with intracellular delay and CTL immune response delay, J. Math. Anal. Appl., 459 (2018), 506-527.
doi: 10.1016/j.jmaa.2017.10.027. |
[37] |
D. Wodarz, J. P. Christensen and A. R. Thomsen,
The importance of lytic and nonlytic immune responses in viral infections, Trend in Immunology, 23 (2002), 194-200.
doi: 10.1016/S1471-4906(02)02189-0. |
[38] |
D. Wodarz and M. A. Nowak,
Immune response and viral phenotype: Do replication rate and cytopathogenicity influence virus load?, Comput. Math. Method. M., 2 (2000), 113-127.
doi: 10.1080/10273660008833041. |
show all references
References:
[1] |
E. Avila-Vales, N. Chan-Chí and G. García-Almeida,
Analysis of a viral infection model with immune impairment, intracellular delay and general non-linear incidence rate, Chaos Solitons Fractals, 69 (2014), 1-9.
doi: 10.1016/j.chaos.2014.08.009. |
[2] |
C. Bartholdy, J. P. Christensen, D. Wodarz and A. R. Thomsen,
Persistent virus infection despite chronic cytotoxic T-lymphocyte activation in gamma interferon-deficient mice infected with lymphocytic choriomeningitis virus, J. Virol., 74 (2000), 10304-10311.
|
[3] |
A. Carpentier, et al., Modes of human T cell leukemia virus type 1 transmission, replication
and persistence, Viruses, 7 (2015), 3603–3624. |
[4] |
P. H. Crowley and E. K. Martin,
Functional responses and interference within and between year classes of a dragonfly population, J. N. Am. Benthol. Soc., 8 (1989), 211-221.
|
[5] |
R. V. Culshaw, S. G. Ruan and G. Webb,
A mathematical model of cell-to-cell spread of HIV-1 that includes a time delay, J. Math. Biol., 46 (2003), 425-444.
doi: 10.1007/s00285-002-0191-5. |
[6] |
R. J. De Boer, Which of our modeling predictions are robust?, PLoS Comput. Biol., 8 (2012), e10002593, 5 pp.
doi: 10.1371/journal.pcbi.1002593. |
[7] |
D. Ebert, C. D. Zschokke-Rohringer and H. J. Carius,
Dose effects and density-dependent regulation of two microparasites of Daphnia magna, Oecologia, 122 (2000), 200-209.
|
[8] |
A. Gessain and O. Cassar, Epidemiological aspects and world distribution of HTLV-1 infection, Front. Microbiol., 3 (2012), e388. |
[9] |
H. Gómez-Acevedo and M. Y. Li,
Backward bifurcation in a model for HTLV-I infection of CD4$^+$T cells, Bull. Math. Biol., 67 (2005), 101-114.
doi: 10.1016/j.bulm.2004.06.004. |
[10] |
J. K. Hale and S. M. Verduyn Lunel, Introduction to Functional Differential Equations, Appl. Math. Sci. 99, Springer-Verlag, New York, 1993.
doi: 10.1007/978-1-4612-0873-0. |
[11] |
J. K. Hale and J. Kato,
Phase space for retarded equation with infinite delay, Funkcial. Ekvac., 21 (1978), 11-41.
|
[12] |
Y. Hino, S. Murakami and T. Naito, Functional-Differential Equations With Infinite Delay, Lecture Notes in Math., 1473. Springer-Verlag, Berlin, 1991.
doi: 10.1007/978-1-4612-0873-0. |
[13] |
D. D. Ho, A. U. Neumann, A. S. Perelson, W. Chen, J. M. Leonard and M. Markowitz,
Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection, Nature, 373 (1995), 123-126.
|
[14] |
S. Jacobson,
Immunopathogenesis of HTLV-I associated neurological disease, J. Infect. Dis., 186 (2002), 187-192.
|
[15] |
Y. Ji and L. Liu,
Global stability of a delayed viral infection model with nonlinear immune response and general incidence rate, Discrete Contin. Dyn. Syst. Ser. B, 21 (2016), 133-149.
doi: 10.3934/dcdsb.2016.21.133. |
[16] |
J. P. La Salle, The Stability of Dynamical Systems, Regional Conference Series in Applied Mathematics, SIAM, Philadelphia, 1976. |
[17] |
X. L. Lai and X. F. Zou,
Modeling HIV-1 virus dynamics with both virus-to-cell infection and cell-to-cell transmission, SIAM J. Math. Anal., 74 (2014), 898-917.
doi: 10.1137/130930145. |
[18] |
B. R. Levin, M. Lipsitch and S. Bonhoeffer,
Population biology, evolution, and infectious disease: Convergence and synthesis, Science, 283 (1999), 806-809.
doi: 10.1126/science.283.5403.806. |
[19] |
S. M. Li and Y. C. Zhou,
Backward bifurcation of an HTLV-I model with immune response, Discrete Contin. Dyn. Syst. Ser. B, 21 (2016), 863-881.
doi: 10.3934/dcdsb.2016.21.863. |
[20] |
M. Y. Li and H. Y. Shu,
Multiple stable periodic oscillations in a mathematical model of CTL response to HTLV-I infection, Bull. Math. Biol., 73 (2011), 1774-1793.
doi: 10.1007/s11538-010-9591-7. |
[21] |
M. Y. Li and H. Y. Shu,
Global dynamics of a mathematical model for HTLV-I infection of CD4$^+$ T cells with delayed CTL response, Nonlinear Anal. RWA, 13 (2012), 1080-1092.
doi: 10.1016/j.nonrwa.2011.02.026. |
[22] |
X. J. Lu, L. L. Hui, S. Q. Liu and J. Li,
A mathematical model of HTLV-I infection with two time delays, Math. Biosci. Eng., 12 (2015), 431-449.
doi: 10.3934/mbe.2015.12.431. |
[23] |
N. MacDonald, Time Lags in Biological Models, Lecture Notes in Biomathematics, 27. Spring-Verlag, Heidelberg, 1978.
doi: 10.1007/978-1-4612-0873-0. |
[24] |
S. Marino, I. B. Hogue, C. J. Ray and D. E. Kirschner,
A methodology for performing global uncertainty and sensitivity analysis in systems biology, J. Theoret. Biol., 254 (2008), 178-196.
doi: 10.1016/j.jtbi.2008.04.011. |
[25] |
J. E. Mittler, B. Sulzer ac, A. U. Neumann ade and A. S. Perelson a,
Influence of delayed viral production on viral dynamics in HIV-1 infected patients, Math. Biosci., 152 (1998), 143-163.
doi: 10.1016/S0025-5564(98)10027-5. |
[26] |
Y. Nakata, Y. Enatsu and Y. Muroya, Complete global dynamics of a delayed viral infection model with lytic and nonlytic effectors, SeMA J., (2012), 27–50. |
[27] |
M. A. Nowak and C. R. M. Bangham,
Population dynamics of immune responses to persistent viruses, Science, 272 (1996), 74-79.
doi: 10.1126/science.272.5258.74. |
[28] |
C. M. Rooney, C. Y. C. Ng, S. Loftin, C. A. Smith, C. Li, R. A. Krance, M. K. Brenner, H. E. Heslop, C. M. Rooney, M. K. Brenner, M. K. Brenner, R. A. Krance and H. E. Heslop,
Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation, Lancet, 345 (1995), 9-13.
doi: 10.1016/S0140-6736(95)91150-2. |
[29] |
H. Y. Shu, L. Wang and J. Watmough,
Global stability of a nonlinear viral infection model with infinitely distributed intracellular delays and CTL immune responses, SIAM J. Appl. Math., 73 (2013), 1280-1302.
doi: 10.1137/120896463. |
[30] |
R. P. Sigdel and C. C. McCluskey,
Global stability for an SEI model of infectious disease with immigration, Appl. Math. Comput., 243 (2014), 684-689.
doi: 10.1016/j.amc.2014.06.020. |
[31] |
N. I. Stilianakis and J. Seydel,
Modeling the T-cell dynamics and pathogenesis of HTLV-I infection, Bull. Math. Biol., 61 (1999), 935-947.
doi: 10.1006/bulm.1999.0117. |
[32] |
C. Vargas-De-León,
Global properties for a virus dynamics model with lytic and nonlytic immune responses and nonlinear immune attack rates, J. Biol. Syst., 22 (2014), 449-462.
doi: 10.1142/S021833901450017X. |
[33] |
J. L. Wang, M. Guo, X. N. Liu and Z. T. Zhao,
Threshold dynamics of HIV-1 virus model with cell-to-cell transmission, cell-mediated immune responses and distributed delay, Appl. Math. Comput., 291 (2016), 149-161.
doi: 10.1016/j.amc.2016.06.032. |
[34] |
K. F. Wang, W. D. Wang and X. N. Liu,
Global stability in a viral infection model with lytic and nonlytic immune responses, Comput. Math. Appl., 51 (2006), 1593-1610.
doi: 10.1016/j.camwa.2005.07.020. |
[35] |
S. L. Wang, X. Y. Song and Z. H. Ge,
Dynamics analysis of a delayed viral infection model with immune impairment, Appl. Math. Model., 35 (2011), 4877-4885.
doi: 10.1016/j.apm.2011.03.043. |
[36] |
Y. Wang, J. Liu and J. M. Heffernan,
Viral dynamics of an HTLV-I infection model with intracellular delay and CTL immune response delay, J. Math. Anal. Appl., 459 (2018), 506-527.
doi: 10.1016/j.jmaa.2017.10.027. |
[37] |
D. Wodarz, J. P. Christensen and A. R. Thomsen,
The importance of lytic and nonlytic immune responses in viral infections, Trend in Immunology, 23 (2002), 194-200.
doi: 10.1016/S1471-4906(02)02189-0. |
[38] |
D. Wodarz and M. A. Nowak,
Immune response and viral phenotype: Do replication rate and cytopathogenicity influence virus load?, Comput. Math. Method. M., 2 (2000), 113-127.
doi: 10.1080/10273660008833041. |


Para.(Unit) | Description | Value | Range | Ref. |
The recruitment rate of healthy T-cells | [10,200] | [20,21,22,34,37] | ||
The death rate of healthy T-cells | [0.01, 0.2] | [20,21,22,34,37] | ||
Viral infectivity rate | [0.001, 0.05] | [20,21,22,34,37] | ||
The death rate of infected not productive cells | [0.01, 0.2] | [36] | ||
The intracellular latent delay | [0, 10] | [1] | ||
The sum of the released rate of viral particles and the death rate of infected T-cells | [0.01, 0.2] | [20,21,22,34,37] | ||
The efficacy of NL-CTL response | [0, 1] | [34,37] | ||
The strength of L-CTL response | [0, 1] | [20,21,22,34,37] | ||
The proliferation rate of CTLs | [0, 1] | [20,21,22,34,37] | ||
The decay rate of CTLs | [0, 1] | [20,21,22,34,37] | ||
|
A fraction of cells newly infected by contacts that survive the antibody immune response | [0, 1] | [9,22] | |
The inhibitory rate from healthy T-cells | [0, 10] | Estimated | ||
The inhibitory rate from infected T-cells | [0, 10] | Estimated | ||
The inhibitory rate from NL-CTL response | [0, 10] | [32] | ||
Immune impairment rate of virus | [0, 1] | [1] |
Para.(Unit) | Description | Value | Range | Ref. |
The recruitment rate of healthy T-cells | [10,200] | [20,21,22,34,37] | ||
The death rate of healthy T-cells | [0.01, 0.2] | [20,21,22,34,37] | ||
Viral infectivity rate | [0.001, 0.05] | [20,21,22,34,37] | ||
The death rate of infected not productive cells | [0.01, 0.2] | [36] | ||
The intracellular latent delay | [0, 10] | [1] | ||
The sum of the released rate of viral particles and the death rate of infected T-cells | [0.01, 0.2] | [20,21,22,34,37] | ||
The efficacy of NL-CTL response | [0, 1] | [34,37] | ||
The strength of L-CTL response | [0, 1] | [20,21,22,34,37] | ||
The proliferation rate of CTLs | [0, 1] | [20,21,22,34,37] | ||
The decay rate of CTLs | [0, 1] | [20,21,22,34,37] | ||
|
A fraction of cells newly infected by contacts that survive the antibody immune response | [0, 1] | [9,22] | |
The inhibitory rate from healthy T-cells | [0, 10] | Estimated | ||
The inhibitory rate from infected T-cells | [0, 10] | Estimated | ||
The inhibitory rate from NL-CTL response | [0, 10] | [32] | ||
Immune impairment rate of virus | [0, 1] | [1] |
Para. | Distribution1 | PRCC1 | p-value1 | Distribution2 | PRCC2 | p-value2 | Rank | |
|
U(10, 200) | |
|
N(105, 30) | |
|
7 | |
|
U(0.01, 0.2) | |
|
N(0.11, 0.03) | |
|
8 | |
|
U(0.001, 0.05) | |
|
N(0.026, 0.005) | |
|
4 | |
|
U(0, 10) | |
|
N(5, 1.667) | |
|
3 | |
|
U(0, 1) | |
|
N(0.5, 0.167) | |
|
1 | |
|
U(0.01, 0.2) | |
|
N(0.11, 0.03) | |
|
6 | |
|
U(0, 10) | |
|
N(5, 1.667) | |
|
5 | |
|
U(0.01, 0.2) | |
|
N(1.005, 0.332) | |
|
2 |
Para. | Distribution1 | PRCC1 | p-value1 | Distribution2 | PRCC2 | p-value2 | Rank | |
|
U(10, 200) | |
|
N(105, 30) | |
|
7 | |
|
U(0.01, 0.2) | |
|
N(0.11, 0.03) | |
|
8 | |
|
U(0.001, 0.05) | |
|
N(0.026, 0.005) | |
|
4 | |
|
U(0, 10) | |
|
N(5, 1.667) | |
|
3 | |
|
U(0, 1) | |
|
N(0.5, 0.167) | |
|
1 | |
|
U(0.01, 0.2) | |
|
N(0.11, 0.03) | |
|
6 | |
|
U(0, 10) | |
|
N(5, 1.667) | |
|
5 | |
|
U(0.01, 0.2) | |
|
N(1.005, 0.332) | |
|
2 |
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