Modelling viral and immune system dynamics

Nature Reviews Immunology

Volumn 2, Issue 1, 2002, Pages 28-36

  Perelson, Alan S ^a  

^a LOS ALAMOS NATIONAL LABORATORY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERFERON; MAJOR HISTOCOMPATIBILITY ANTIGEN; TETRAMER; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT;

ANTIVIRAL ACTIVITY; CHEMICAL LABELING; CYTOMEGALOVIRUS; DATA ANALYSIS; DENDRITIC CELL; DYNAMICS; EXPERIMENT; FOLLICULAR DENDRITIC CELL; HEPATITIS B VIRUS; HEPATITIS C VIRUS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; IMMUNE RESPONSE; IMMUNE SYSTEM; INFECTION RATE; INFECTION SENSITIVITY; KINETICS; LYMPHOCYTE; LYMPHOCYTE COUNT; MATHEMATICAL MODEL; NONHUMAN; NONLINEAR REGRESSION ANALYSIS; PRIORITY JOURNAL; REVIEW; T LYMPHOCYTE; VIRAL SET POINT; VIRUS CONCENTRATION; VIRUS INFECTION; ANIMAL; BIOLOGICAL MODEL; DRUG EFFECT; HEPATITIS B; HEPATITIS C; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOLOGY; ISOLATION AND PURIFICATION; PATHOLOGY; PHYSIOLOGY; VIROLOGY; VIRUS REPLICATION;

ANIMALS; ANTI-HIV AGENTS; HEPATITIS B; HEPATITIS C; HIV INFECTIONS; HIV-1; HUMANS; MODELS, IMMUNOLOGICAL; T-LYMPHOCYTES; VIRUS DISEASES; VIRUS REPLICATION;

EID: 0036371443     PISSN: 14741733     EISSN: None     Source Type: Journal    
DOI: 10.1038/nri700     Document Type: Review

References (101)

1. Perelson, A. S. & Weisbuch, G. Immunology for physicists. Rev. Mod. Phys. 69, 1219-1267 (1997). Extensive review of modelling in immunology.
2. Perelson, A. S. & Oster, G. F. Theoretical studies of clonal selection: minimal antibody repertoire size and reliability of self-non-self discrimination. J. Theor. Biol. 81, 645-670 (1979).
3. Perelson, A. S. in Cell Surface Dynamics: Concepts and Models (eds Perelson, A. S., DeLisi, C. & Weigel, F. W.) 223-276 (Marcel Dekker, New York, 1984).
4. Kepler, T. B. & Perelson, A. S., Cyclic re-entry of germinal center B cells and the efficiency of affinity maturation. Immunol. Today 14, 412-415 (1993).
5. De Boer, R. J. & Perelson, A. S. How diverse should the immune system be? Proc. R. Soc. Lond. B 252, 171-175 (1993).
6. Percus, J. K., Percus, O. E. & Perelson, A. S. Predicting the size of the T-cell receptor and antibody combining region from consideration of efficient self-nonself discrimination. Proc. Natl Acad. Sci. USA 90, 1691-1695 (1993).
7. McKeithan, T. W. Kinetic proofreading in T-cell receptor signal transduction. Proc. Natl Acad. Sci. USA 92, 5042-5046 (1995).
8. McLean, A. R., Rosado, M. M., Agenes, F., Vasconcellos, R. & Freitas, A. A. Resource competition as a mechanism for B cell homeostasis. Proc. Natl Acad. Sci. USA 94, 5792-5797 (1997).
9. Borghans, J. A., De Boer, R. J., Sercarz, E. & Kumar, V. T cell vaccination in experimental autoimmune encephalomyelitis: a mathematical model. J. Immunol. 161, 1087-1093 (1998).
10. Smith, D. J., Forrest, S., Ackley, D. H. & Perelson, A. S. Variable efficacy of repeated annual influenza vaccination. Proc. Natl Acad. Sci. USA 96, 14001-14006 (1999). Shows, through a large-scale simulation model of the humoral immune response, that variable efficacy of influenza vaccine in repeat vaccinees can be explained by a memory response to a prior vaccine or infection; that is, original antigenic sin.
11. Detours, V. & Perelson, A. S. Explaining high alloreactivity as a quantitative consequence of affinity-driven thymocyte selection. Proc. Natl Acad. Sci. USA 96, 5153-5158 (1999).
12. Kesmir, C. & De Boer, R. J. A mathematical model on germinal center kinetics and termination. J. Immunol. 163, 2463-2469 (1999).
13. Borghans, J. A., Taams, L. S., Wauben, M. H. & de Boer, R. J. Competition for antigenic sites during T cell proliferation: a mathematical interpretation of in vitro data. Proc Natl Acad. Sci. USA 96, 10782-10787 (1999).
14. Borghans, J. A., Noest, A. J. & De Boer, R. J. How specific should immunological memory be? J. Immunol. 163, 569-575 (1999).
15. Segel, L. A. & Bar-Or, R. L. On the role of feedback in promoting conflicting goals of the adaptive immune system. J. Immunol. 163, 1342-1349 (1999).
16. Detours, V. & Perelson, A. S. The paradox of alloreactivity and self MHC restriction: quantitative analysis and statistics. Proc. Natl Acad. Sci. USA 97, 8479-8483 (2000).
17. Hlavacek, W. S., Redondo, A., Metzger, H., Wofsy, C. & Goldstein, B. Kinetic proofreading models for cell signaling predict ways to escape kinetic proofreading. Proc. Natl Acad. Sci. USA 98, 7295-7300 (2001).
18. Ho, D. D. et al. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373, 123-126 (1995).
19. Wei, X. et al. Viral dynamics in human immunodeficiency virus type 1 infection. Nature 373, 117-122 (1995). References 18 and 19 are the key papers showing that HIV replicates and is cleared rapidly during chronic HIV-1 infection.
20. + lymphocytes and the rate of clearance of free virions.
21. Coffin, J. M. HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science 267, 483-489 (1995).
22. Wain-Hobson, S. AIDS. Virological mayhem. Nature 373, 102 (1995).
23. + lymphocytes in vivo. AIDS 11, S17-S24 (1997).
24. Nowak, M. A. & May, R. M. Virus Dynamics: Mathematical Principles of Immunology and Virology (Oxford Univ. Press, 2000). Monograph that reviews the field of viral dynamic modelling.
25. Ho, D. D. Viral counts count in HIV infection. Science 272, 1124-1125 (1996).
26. Perelson, A. S. & Nelson, P. W. Mathematical analysis of HIV-1 dynamics in vivo. SIAM Rev. 41, 3-44 (1999). A review of the mathematics used in modelling HIV infection.
27. Wu, H., Ruan, P., Ding, A. A., Sullivan, J. L. & Luzuriaga, K. Inappropriate model-fitting methods may lead to significant underestimates of viral decay rates in HIV dynamic studies. J. Acquir. Immune Defic. Syndr. 21, 426-428 (1999).
28. Ramratnam, B. et al. Rapid production and clearance of HIV-1 and hepatitis C virus assessed by large volume plasma apheresis. Lancet 354, 1782-1785 (1999).
29. Mansky, L. M. & Temin, H. M. Lower in vivo mutation rate of human immunodeficiency virus type 1 than that predicted from the fidelity of purified reverse transcriptase. J. Virol. 69, 5087-5094 (1995).
30. Bonhoeffer, S., May, R. M., Shaw, G. M. & Nowak, M. A. Virus dynamics and drug therapy. Proc. Natl Acad. Sci. USA 94, 6971-6976 (1997).
31. Wein, L. M., D'Amato, R. M. & Perelson, A. S. Mathematical analysis of antiretroviral therapy aimed at HIV-1 eradication of maintenance of low viral loads. J. Theor. Biol. 192, 81-98 (1998).
32. Ding, A. A. & Wu, H. Relationships between antiviral treatment effects and biphasic viral decay rates in modeling HIV dynamics Math. Biosci. 160, 63-82 (1999).
33. Mueller, B. U. et al. Individual prognoses of long-term responses to antiretroviral treatment based on virological, immunological and pharmacological parameters measured during the first week under therapy. AIDS 12, F191-F196 (1998).
34. Mittler, J. et al. Short-term measures of relative efficacy predict longer-term reductions in human immunodeficiency virus type 1 RNA levels following nelfinavir monotherapy. Antimicrob. Agents Chemother. 45, 1438-1443 (2001).
35. Louie, M. et al. Using viral dynamics to document the greater antiviral potency of a regime containing lopinavir/ritonavir, efavirenz, tenofovir, and lamivudine relative to standard therapy. 8th Conf. Retroviruses Opportunistic Infect. Abstr. 383 (2001).
36. Perelson, A. S. et al. Decay characteristics of HIV-1-infected compartments during combination therapy. Nature 387, 188-191 (1997). This paper reported that the decline in plasma HIV-1 RNA after the initiation of therapy has two phases. The second phase was attributed to long-lived infected cells, release of virus from tissue reservoirs, or the activation of latently infected cells. Indicates that the cells responsible for the second phase could be eradicated after 2-3 years of 100% effective therapy.
37. Finzi, D. et al. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 278, 1295-1300 (1997).
38. Chun, T. W. et al. Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 387, 183-188 (1997).
39. Zhang. L. et al. Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. N. Engl. J. Med. 340, 1605-1613 (1999).
40. + T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nature Med. 5, 512-517 (1999).
41. Wong, J. K. et al. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science 278, 1291-1295 (1997).
42. Chun, T. W. et al. Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. Proc. Natl Acad. Sci. USA 94, 13193-13197 (1997).
43. Furtado, M. R. et al. Persistence of HIV-1 transcription in peripheral-blood mononuclear cells in patients receiving potent antiretroviral therapy. N Engl J. Med. 340, 1614-1622 (1999).
44. Dornadula, G. et al. Residual HIV-1 RNA in blood plasma of patients taking suppressive highly active antiretroviral therapy. J. Am. Med. Assoc. 282, 1627-1632 (1999).
45. Sharkey, M. E. et al. Persistence of episomal HIV-1 infection intermediates in patients on highly active anti-retroviral therapy. Nature Med. 6, 76-81 (2000).
46. Siliciano, J. D. & Siliciano, R. F. Latency and viral persistence in HIV-1 infection. J. Clin. Invest. 106, 823-825 (2000).
47. Hlavacek, W. S., Wofsy, C. & Perelson, A. S. Dissociation of HIV-1 from follicular dendritic cells during HAART: mathematical analysis. Proc. Natl Acad. Sci. USA 96, 14681-14686 (1999). Shows that complete elimination of HIV-1 from follicular dendritic cells can take as long as a decade if virions do not degrade.
48. Hlavacek, W. S., Stilianakis, N. I., Notermans, D. W., Danner, S. A. & Perelson, A. S. Influence of follicular dendritic cells on decay of HIV during antiretroviral therapy. Proc. Natl. Acad. Sci. USA 97, 10966-10971 (2000).
49. Hlavacek, W. S., Stilianakis, N. I. & Perelson, A. S. Influence of follicular dendritic cells on HIV dynamics. Phil. Trans. R. Soc. Lond. B 355, 1051-1058 (2000).
50. Smith, B. A. et al. Persistence of infectious HIV on follicular dendritic cells. J. Immunol. 166, 690-696 (2001).
51. Neumann, A. U. et al. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-α therapy. Science 282, 103-107 (1998). Shows that HCV, like HIV, has rapid production and clearance. Also indicates that interferon causes rapid HCV clearance mainly by blocking production of virions from infected cells in a dose-dependent manner.
52. Bekkering, F. C. et al. Ultrarapid hepatitis C virus clearance by daily high-dose interferon in non-responders to standard therapy. J. Hepatol. 28, 960-964 (1998).
53. Yasui, K. et al. Dynamics of hepatitis C viremia following interferon-α administration. J. Infect. Dis. 177, 1475-1479 (1998).
54. Neumann, A. U. et al. Differences in viral dynamics between genotypes 1 and 2 of hepatitis C virus. J. Infect. Dis. 182, 28-35 (2000).
55. Nowak, M. A. et al. Viral dynamics in hepatitis B virus infection. Proc. Natl Acad. Sci. USA 93, 4398-4402 (1996). First paper to analyse the dynamics of HBV infection.
56. Tsiang, M., Rooney, J. F., Toole, J. J. & Gibbs, C. S. Biphasic clearance kinetics of hepatitis B virus from patients during adefovir dipivoxil therapy. Hepatology 29, 1863-1869 (1999).
57. Lau, G. K. et al. Combination therapy with lamivudine and famciclovir for chronic hepatitis B-infected Chinese patients: a viral dynamics study. Hepatology 32, 394-399 (2000).
58. Lewin, S. R. et al. Analysis of hepatitis B viral load decline under potent therapy: complex decay profiles observed. Hepatology 34, 1012-1020 (2001).
59. Guidotti, L. G. et al. Viral clearance without destruction of infected cells during acute HBV infection. Science 284, 825-829 (1999).
60. Whalley, S. A. et al. Kinetics of acute hepatitis B virus infection in humans. J. Exp. Med. 198, 847-854 (2001).
61. Emery, V. C., Cope, A. V., Bowen, E. F., Gor D. & Griffiths, P. D. The dynamics of human cytomegalovirus replication in vivo. J. Exp. Med. 190, 177-182 (1999).
62. Emery, V. C. & Griffiths, P. D. Prediction of cytomegalovirus load and resistance patterns after antiviral chemotherapy. Proc. Natl Acad. Sci. USA 97, 8039-8044 (2000).
63. Phillips, A. N. Reduction of HIV concentration during acute infection: independence from a specific immune response. Science 271, 497-499 (1996).
64. Nowak, M. A. & Bangham, C. R. Population dynamics of immune responses to persistent viruses. Science 272, 74-79 (1996).
65. Koup, R. A. et al. Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J. Virol. 68, 4650-4655 (1994).
66. Stafford, M. A. et al. Modeling plasma virus concentration during primary HIV infection. J. Theor. Biol. 203, 285-301 (2000).
67. Welsh, R. M. Assessing CD8 T cell number and dysfunction in the presence of antigen. J. Exp. Med. 193, F19-F22 (2001).
68. + T cells with a defect in effector function that is reversible on extended interleukin-2 incubation. J. Virol. 75, 3028-3033 (2001).
69. Ahmed, R., Salmi, A., Butler, L. D., Chiller, J. M. & Oldstone, M. B. Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice. Role in suppression of cytotoxic T lymphocyte response and viral persistence. J. Exp. Med. 160, 521-540 (1984).
70. Walsh, C. M. et al. Immune function in mice lacking the perforin gene. Proc. Natl Acad. Sci. USA 91, 10854-10858 (1994).
71. + T cell response to LCMV. J. Virol. 75, 10663-10669 (2001).
72. Bocharov, G. A. Modelling the dynamics of LCMV infection in mice: conventional and exhaustive CTL responses. J. Theor. Biol. 192, 283-308 (1998).
73. Dahari, H., Major, M., Mihalik, K., Feinstone, S. & Neumann, A. U. Lack of virus cytopathicity but strong IFN and cellular immune responses during primary HCV infections in chimpanzees. Hepatology 32, 302A (2000).
74. Altman, J. D. et al. Phenotypic analysis of antigen-specific T lymphocytes. Science 274, 94-96 (1996).
75. Wodarz, D. et al. A new theory of cytotoxic T-lymphocyte memory: implications for HIV treatment. Phil. Trans. R. Soc. Lond. B 355, 329-343 (2000).
76. Wodarz, D. & Nowak, M. A. Correlates of cytotoxic T-lymphocyte-mediated virus control: implications for immunosuppressive infections and their treatment. Phil. Trans. R. Soc. Lond. B 355, 1059-1070 (2000).
77. Wodarz, D. & Jansen, V. A. The role of T cell help for antiviral CTL responses. J. Theor. Biol. 211, 419-432 (2001).
78. Mellors, J. W. et al. Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science 272, 1167-1170 (1996).
79. Muller, V., Maree, A. F. M. & De Boer, R. J. Small variations in multiple parameters account for wide variations in HIV-1 set points: a novel modelling approach. Proc. R. Soc. Lond. B 268, 235-242 (2000).
80. + lymphocytes. Science 283, 857-860 (1999).
81. + T cell depletion in simian immunodeficiency virus-infected macaques. J. Exp. Med. 189, 991-998 (1999).
82. + T cells. Science 270, 1811-1815 (1995).
83. + T cells suppress human immunodeficiency virus replication by inhibiting viral transcription. Proc. Natl Acad. Sci. USA 92, 2308-2312 (1995).
84. Herz, A. V., Bonhoeffer, S., Anderson, R. M., May, R. M. & Nowak, M. A. Viral dynamics in vivo: limitations on estimates of intracellular delay and virus decay. Proc. Natl Acad. Sci. USA 93, 7247-7251 (1996).
85. Mittler, J. E., Sulzer, B., Neumann, A. U. & Perelson, A. S. Influence of delayed viral production on viral dynamics in HIV-1 infected patients. Math. Biosci. 152, 143-163 (1998).
86. Mittler, J. E., Markowitz, M., Ho, D. D. & Perelson, A. S. Improved estimates for HIV-1 clearance rate and intracellular delay. AIDS 13, 1415-1417 (1999).
87. Nelson, P. W., Murray, J. D. & Perelson, A. S. A model of HIV-1 pathogenesis that includes an intracellular delay. Math. Biosci. 163, 201-215 (2000).
88. Nelson, P. W., Mittler, J. E. & Perelson, A. S. Effect of drug efficacy and the eclipse phase of the viral life cycle on estimates of HIV viral dynamic parameters. J. Acquir. Immune Defic. Syndr. 26, 405-412 (2001).
89. Levy, J. A. HIV and the Pathogenesis of AIDS (American Society for Microbiology, Washington DC, 1998).
90. Macallan, D. C. et al. Measurement of cell proliferation by labeling of DNA with stable isotope-labeled glucose: studies in vitro, in animals, and in humans. Proc. Natl Acad. Sci. USA 95, 708-713 (1998).
91. Hellerstein, M. K. Measurement of T-cell kinetics: recent methodologic advances. Immunol. Today 20, 438-441 (1999).
92. Mohri, H., Bonhoeffer, S., Monard, S., Perelson, A. S. & Ho, D. D. Rapid turnover of T lymphocytes in SIV-infected rhesus macaques. Science 279, 1223-1227 (1998).
93. Mohri, H. et al. Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy. J. Exp. Med. 194, 1277-1287 (2001). T-cell kinetics in uninfected and HIV-infected humans determined by stable isotope labelling and modelling of the labelling kinetics.
94. McCune, J. M. et al. Factors influencing T-cell turnover in HIV-1-seropositive patients. J. Clin. Invest. 105, R1-R8 (2000).
95. Bonhoeffer, S., Mohri, H., Ho, D. & Perelson, A. S. Quantification of cell turnover kinetics using 5-bromo-2′-deoxyuridine. J. Immunol. 164, 5049-5054 (2000).
96. Hellerstein, M. et al. Directly measured kinetics of circulating T lymphocytes in normal and HIV-1-infected humans. Nature Med. 5, 83-89 (1999).
97. Rouzine, I. M. & Coffin, J. M. T cell turnover in SIV infection. Science 284, 555b (1999).
98. Grossman, Z., Herberman, R. B. & Dimitrov, D. S. T cell turnover in SIV infection. Science 284, 555a (1999).
99. Celada, F. & Seiden, P. E. A computer model of cellular interactions in the immune system. Immunol. Today 13, 56-62 (1992).
100. Smith, D. J., Forrest, S., Ackley, D. H. & Perelson, A. S. Using lazy evaluation to simulate realistic-size repertoires in models of the immune system. Bull. Math. Biol. 60, 647-658 (1998).
101. Ribiero, R., Mohn, H., Ho, D. D. & Perelson, A. S. Modeling deuterated glucose labeling of T lymphocytes. Bull. Math. Biol. (in the press).