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A mathematical model of HIV dynamics in the presence of a rescuing virus with replication deficiency

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Abstract

Recently, an enzyme (Cre recombinase) has been developed by directed evolution that successfully removes the HIV genome from the nuclear DNA of infected cells. To explore this idea further, we hypothesized that a replication deficient virus (called “police virus”), added externally, can deliver such a recombinase which excises the integrated HIV DNA from the genome of infected cells. Such a “police virus” could attack and remove the integrated provirus which is not possible using contemporary strategies. The hypothesis was tested by developing a mathematical model that describes the dynamics of virus-host cell interaction and the consequences of introducing the “police virus”. The simulations show that such a therapeutic vector may eradicate all HIV viruses from the system in the long term. All components of the HIV infection (free virus, latently, and actively infected cells) can be cleared and the system ends up only with susceptible CD4+ cells. The proposed model may provide new insights in the dynamical behavior and future alternative treatments of HIV.

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References

  • Bailey J, Blankson JN, Wind-Rotolo M, Siliciano RF (2004) Mechanisms of HIV-1 escape from immune responses and antiretroviral drugs. Curr Opin Immunol 16:470–476

    Article  PubMed  CAS  Google Scholar 

  • Berencsi G, Minárovits J, Nász I, Földes I (1989) Prospects for the control of AIDS patients by introducing defective-HIV harbouring leukocytes. Med Hypotheses 30:223–228

    Article  PubMed  CAS  Google Scholar 

  • Capodici J, Karikó K, Weissman D (2002) Inhibition of HIV-1 infection by small interfering RNA-mediated RNA interference. J Immunol 169:5196–5201

    PubMed  Google Scholar 

  • Chun TW, Fauci AS (1999) Latent reservoirs of HIV: obstacles to the eradication of virus. Proc Natl Acad Sci USA 96:10958–10961

    Article  PubMed  CAS  Google Scholar 

  • Di Mascio M, Ribeiro RM, Markowitz M, Ho DD, Perelson AS (2004) Modeling the long-term control of viremia in HIV-1 infected patients treated with antiretroviral therapy. Math Biosci 188:47–62

    Article  PubMed  CAS  Google Scholar 

  • Dropulić B, Hĕrmánková M, Pitha PM (1996) A conditionally replicating HIV-1 vector interferes with wild-type HIV-1 replication and spread. Proc Natl Acad Sci USA 93:11103–11108

    Article  PubMed  Google Scholar 

  • Finzi D, Blankson J, Siliciano JD, Margolick JB, Chadwick K, Pierson T, Smith K, Lisziewicz J, Lori F, Flexner C, Quinn TC, Chaisson RE, Rosenberg E, Walker B, Gange S, Gallant J, Siliciano RF (1999) Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med 5:512–517

    Article  PubMed  CAS  Google Scholar 

  • Han Y, Wind-Rotolo M, Yang HC, Siliciano JD, Siliciano RF (2007) Experimental approaches to the study of HIV-1 latency. Nat Rev Microbiol 5:95–106

    Article  PubMed  CAS  Google Scholar 

  • Johnson RP (2002) Mechanisms of protection against simian immunodeficiency virus infection. Vaccine 20:1985–1987

    Article  PubMed  CAS  Google Scholar 

  • Johnson RP (2006) HIV pathogenesis and vaccine development. Top HIV Med 14:8–15

    PubMed  Google Scholar 

  • Klipp E, Herwig R, Kowald A, Wierling C (2009) Systems biology. Wiley, New York

    Google Scholar 

  • Landi A, Mazzoldi A, Andreoni C, Bianchi M, Cavallini A, Laurino M, Ricotti L, Iuliano R, Matteoli B, Ceccherini-Nelli L (2008) Modelling and control of HIV dynamics. Comput Methods Programs Biomed 89:162–168

    Article  PubMed  Google Scholar 

  • Layden TJ, Layden JE, Ribeiro RM, Perelson AS (2003) Mathematical modeling of viral kinetics: a tool to understand and optimize therapy. Clin Liver Dis 7:163–178

    Article  PubMed  Google Scholar 

  • Marsden MD, Zack JA (2009) Eradication of HIV: current challenges and new directions. J Antimicrob Chemother 63:7–10

    Article  PubMed  CAS  Google Scholar 

  • Nelson GW, Perelson AS (1995) Modeling defective interfering virus therapy for AIDS: conditions for DIV survival. Math Biosci 125:127–153

    Article  PubMed  CAS  Google Scholar 

  • Nowak MA, Bangham CR (1996) Population dynamics of immune responses to persistent viruses. Science 272:74–79

    Article  PubMed  CAS  Google Scholar 

  • Perelson AS (2002) Modelling viral and immune system dynamics. Nat Rev Immunol 2:28–36

    Article  PubMed  CAS  Google Scholar 

  • Phillips AN (1996) Reduction of HIV concentration during acute infection: independence from a specific immune response. Science 271:497–499

    Article  PubMed  CAS  Google Scholar 

  • Pierson T, McArthur J, Siliciano RF (2000) Reservoirs for HIV-1: mechanisms for viral persistence in the presence of antiviral immune responses and antiretroviral therapy. Annu Rev Immunol 18:665–708

    Article  PubMed  CAS  Google Scholar 

  • Qin XF, An DS, Chen IS, Baltimore D (2003) Inhibiting HIV-1 infection in human T cells by lentiviral-mediated delivery of small interfering RNA against CCR5. Proc Natl Acad Sci USA 100:183–188

    Article  PubMed  CAS  Google Scholar 

  • Revilla T, García-Ramos G (2003) Fighting a virus with a virus: a dynamic model for HIV-1 therapy. Math Biosci 185:191–203

    Article  PubMed  Google Scholar 

  • Ribeiro RM, Mohri H, Ho DD, Perelson AS (2002) In vivo dynamics of T cell activation, proliferation, and death in HIV-1 infection: why are CD4+ but not CD8+ T cells depleted? Proc Natl Acad Sci USA 99:15572–15577

    Article  PubMed  CAS  Google Scholar 

  • Richman DD, Margolis DM, Delaney M, Greene WC, Hazuda D, Pomerantz RJ (2009) The challenge of finding a cure for HIV infection. Science 323:1304–1307

    Article  PubMed  CAS  Google Scholar 

  • Rong L, Perelson AS (2009) Modeling HIV persistence, the latent reservoir, and viral blips. J Theor Biol 260:308–331

    Article  PubMed  Google Scholar 

  • Rong L, Feng Z, Perelson AS (2007) Emergence of HIV-1 drug resistance during antiretroviral treatment. Bull Math Biol 69:2027–2060

    Article  PubMed  Google Scholar 

  • Rosenberg ES, Altfeld M, Poon SH, Phillips MN, Wilkes BM, Eldridge RL, Robbins GK, D’Aquila RT, Goulder PJ, Walker BD (2000) Immune control of HIV-1 after early treatment of acute infection. Nature 407:523–526

    Article  PubMed  CAS  Google Scholar 

  • Sarkar I, Hauber I, Hauber J, Buchholz F (2007) HIV-1 proviral DNA excision using an evolved recombinase. Science 316:1912–1925

    Article  PubMed  CAS  Google Scholar 

  • Schnell MJ, Johnson JE, Buonocore L, Rose JK (1997) Construction of a novel virus that targets HIV-1-infected cells and controls HIV-1 infection. Cell 90:849–857

    Article  PubMed  CAS  Google Scholar 

  • Siliciano JD, Siliciano RF (2000) Latency and viral persistence in HIV-1 infection. J Clin Investig 106:823–825

    Article  PubMed  CAS  Google Scholar 

  • Staszewski S, Morales-Ramirez J, Tashima KT, Rachlis A, Skiest D, Stanford J, Stryker R, Johnson P, Labriola DF, Farina D, Manion DJ, Ruiz NM (1999) Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. N Engl J Med 341:1865–1873

    Article  PubMed  CAS  Google Scholar 

  • Steinmeyer SH, Wilke CO (2009) Lethal mutagenesis in a structured environment. J Theor Biol 261:67–73

    Article  PubMed  Google Scholar 

  • Wodarz D, Nowak MA (2002) Mathematical models of HIV pathogenesis and treatment. Bioessays 24:1178–1187

    Article  PubMed  Google Scholar 

  • Xia X (2003) Estimation of HIV/AIDS parameters. Automatica 39:1983–1988

    Article  Google Scholar 

  • Zurakowski R, Teel AR (2006) A model predictive control based scheduling method for HIV therapy. J Theor Biol 238:368–382

    Article  PubMed  Google Scholar 

Download references

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Correspondence to Elias Zintzaras.

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The authors contributed equally to this article.

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Zintzaras, E., Kowald, A. A mathematical model of HIV dynamics in the presence of a rescuing virus with replication deficiency. Theory Biosci. 130, 127–134 (2011). https://doi.org/10.1007/s12064-011-0119-y

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  • DOI: https://doi.org/10.1007/s12064-011-0119-y

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