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Proc Biol Sci. Apr 22, 2002; 269(1493): 809–815.
PMCID: PMC1690968

Immune response and virus population composition: HIV as a case study.

Abstract

Based on the current understanding of the immune response, we present what we believe to be a new model of intrahost virus dynamics. The model takes into account the relationship between virus replication rate and the level of antigen displayed by infected cells, and shows how the cell-directed immune response controls both virus load and virus replication rate. In contrast to conventional wisdom, it shows that the predominant virus variant does not necessarily have the highest replication rate. A strong immune response produces a selective advantage for latent viruses, whereas a deteriorating immune response invites in viruses of higher replication rates. The model is analysed in light of the well-studied HIV/AIDS disease progression, and shows how a wide range of major, seemingly unrelated issues in the study of HIV may be accounted for in a simple and unified manner.

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Selected References

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  • Altes HK, Jansen VA. Intra-host competition between nef-defective escape mutants and wild-type human immunodeficiency virus type 1. Proc Biol Sci. 2000 Jan 22;267(1439):183–189. [PMC free article] [PubMed]
  • Bonhoeffer S, Coffin JM, Nowak MA. Human immunodeficiency virus drug therapy and virus load. J Virol. 1997 Apr;71(4):3275–3278. [PMC free article] [PubMed]
  • Bonhoeffer S, May RM, Shaw GM, Nowak MA. Virus dynamics and drug therapy. Proc Natl Acad Sci U S A. 1997 Jun 24;94(13):6971–6976. [PMC free article] [PubMed]
  • Buseyne F, Rivière Y. The flexibility of the TCR allows recognition of a large set of naturally occurring epitope variants by HIV-specific cytotoxic T lymphocytes. Int Immunol. 2001 Jul;13(7):941–950. [PubMed]
  • Callaway DS, Ribeiro RM, Nowak MA. Virus phenotype switching and disease progression in HIV-1 infection. Proc Biol Sci. 1999 Dec 22;266(1437):2523–2530. [PMC free article] [PubMed]
  • Cornelissen M, Mulder-Kampinga G, Veenstra J, Zorgdrager F, Kuiken C, Hartman S, Dekker J, van der Hoek L, Sol C, Coutinho R, et al. Syncytium-inducing (SI) phenotype suppression at seroconversion after intramuscular inoculation of a non-syncytium-inducing/SI phenotypically mixed human immunodeficiency virus population. J Virol. 1995 Mar;69(3):1810–1818. [PMC free article] [PubMed]
  • Del Val M, Schlicht HJ, Ruppert T, Reddehase MJ, Koszinowski UH. Efficient processing of an antigenic sequence for presentation by MHC class I molecules depends on its neighboring residues in the protein. Cell. 1991 Sep 20;66(6):1145–1153. [PubMed]
  • Ercoli L, Sarmati L, Nicastri E, Giannini G, Galluzzo C, Vella S, Andreoni M. HIV phenotype switching during antiretroviral therapy: emergence of saquinavir-resistant strains with less cytopathogenicity. AIDS. 1997 Aug;11(10):1211–1217. [PubMed]
  • Ewald PW. Evolution of mutation rate and virulence among human retroviruses. Philos Trans R Soc Lond B Biol Sci. 1994 Nov 29;346(1317):333–343. [PubMed]
  • Germain RN, Stefanová I. The dynamics of T cell receptor signaling: complex orchestration and the key roles of tempo and cooperation. Annu Rev Immunol. 1999;17:467–522. [PubMed]
  • Greenblatt RM, Jacobson LP, Levine AM, Melnick S, Anastos K, Cohen M, DeHovitz J, Young MA, Burns D, Miotti P, et al. Human herpesvirus 8 infection and Kaposi's sarcoma among human immunodeficiency virus-infected and -uninfected women. J Infect Dis. 2001 Apr 1;183(7):1130–1134. [PubMed]
  • Haase AT. Population biology of HIV-1 infection: viral and CD4+ T cell demographics and dynamics in lymphatic tissues. Annu Rev Immunol. 1999;17:625–656. [PubMed]
  • Kirschner D. Dynamics of co-infection with M. Tuberculosis and HIV-1. Theor Popul Biol. 1999 Feb;55(1):94–109. [PubMed]
  • Lifson JD, Nowak MA, Goldstein S, Rossio JL, Kinter A, Vasquez G, Wiltrout TA, Brown C, Schneider D, Wahl L, et al. The extent of early viral replication is a critical determinant of the natural history of simian immunodeficiency virus infection. J Virol. 1997 Dec;71(12):9508–9514. [PMC free article] [PubMed]
  • May RM, Nowak MA. Coinfection and the evolution of parasite virulence. Proc Biol Sci. 1995 Aug 22;261(1361):209–215. [PubMed]
  • Montoya M, Del Val M. Intracellular rate-limiting steps in MHC class I antigen processing. J Immunol. 1999 Aug 15;163(4):1914–1922. [PubMed]
  • Nowak MA, Bangham CR. Population dynamics of immune responses to persistent viruses. Science. 1996 Apr 5;272(5258):74–79. [PubMed]
  • Nowak MA, May RM. Mathematical biology of HIV infections: antigenic variation and diversity threshold. Math Biosci. 1991 Sep;106(1):1–21. [PubMed]
  • Nowak M, May RM. AIDS pathogenesis: mathematical models of HIV and SIV infections. AIDS. 1993;7 (Suppl 1):S3–18. [PubMed]
  • Nowak MA, May RM. Superinfection and the evolution of parasite virulence. Proc Biol Sci. 1994 Jan 22;255(1342):81–89. [PubMed]
  • Nowak MA, Anderson RM, Boerlijst MC, Bonhoeffer S, May RM, McMichael AJ. HIV-1 evolution and disease progression. Science. 1996 Nov 8;274(5289):1008–1011. [PubMed]
  • Ogg GS, Kostense S, Klein MR, Jurriaans S, Hamann D, McMichael AJ, Miedema F. Longitudinal phenotypic analysis of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes: correlation with disease progression. J Virol. 1999 Nov;73(11):9153–9160. [PMC free article] [PubMed]
  • Ostrowski MA, Krakauer DC, Li Y, Justement SJ, Learn G, Ehler LA, Stanley SK, Nowak M, Fauci AS. Effect of immune activation on the dynamics of human immunodeficiency virus replication and on the distribution of viral quasispecies. J Virol. 1998 Oct;72(10):7772–7784. [PMC free article] [PubMed]
  • Phillips AN. Reduction of HIV concentration during acute infection: independence from a specific immune response. Science. 1996 Jan 26;271(5248):497–499. [PubMed]
  • Price DA, O'callaghan CA, Whelan JA, Easterbrook PJ, Phillips RE. Cytotoxic T lymphocytes and viral evolution in primary HIV-1 infection. Clin Sci (Lond) 1999 Dec;97(6):707–718. [PubMed]
  • Regoes RR, Wodarz D, Nowak MA. Virus dynamics: the effect of target cell limitation and immune responses on virus evolution. J Theor Biol. 1998 Apr 21;191(4):451–462. [PubMed]
  • Telzak EE, Hershow R, Kalish LA, Hardy WD, Jr, Zuckerman E, Levine A, Delapenha R, DeHovitz J, Greenblatt RM, Anastos K. Seroprevalence of HTLV-I and HTLV-II among a cohort of HIV-infected women and women at risk for HIV infection. Women's Interagency HIV Study. J Acquir Immune Defic Syndr Hum Retrovirol. 1998 Dec 15;19(5):513–518. [PubMed]
  • Vijh S, Pilip IM, Pamer EG. Effect of antigen-processing efficiency on in vivo T cell response magnitudes. J Immunol. 1998 Apr 15;160(8):3971–3977. [PubMed]
  • Villanueva MS, Fischer P, Feen K, Pamer EG. Efficiency of MHC class I antigen processing: a quantitative analysis. Immunity. 1994 Sep;1(6):479–489. [PubMed]
  • Wodarz D, Lloyd AL, Jansen VA, Nowak MA. Dynamics of macrophage and T cell infection by HIV. J Theor Biol. 1999 Jan 7;196(1):101–113. [PubMed]
  • Wodarz D, Page KM, Arnaout RA, Thomsen AR, Lifson JD, Nowak MA. A new theory of cytotoxic T-lymphocyte memory: implications for HIV treatment. Philos Trans R Soc Lond B Biol Sci. 2000 Mar 29;355(1395):329–343. [PMC free article] [PubMed]

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