Virus dynamics

Mathematical modeling of within-host HIV Infection dynamics

In the field of within-host HIV modeling (virus dynamics) ordinary differential equation systems are generally used as a framework to evaluate the results of laboratory experiments, to make qualitative predictions about virus dynamics or to compare and test hypotheses related to specific aspects of the infection. We investigated why the rate of virus load decline slows in individuals undergoing antiviral treatment, what are the sources of the immense variability of the virus load in untreated individuals, whether the property of HIV to activate the immune system may be the result of adaptive evolution, and how ‘superinfection‘ with a second strain of the virus can affect the course of infection.

Reaction kinetics of HIV maturation

We used reaction kinetics modeling to better understand the proteolytic cleavage reactions that are crucial for the maturation of HIV virions. We found that the rate of Gag-Pol autoproteolysis and the catalytic rate at the CA/SP1 cleavage site have the greatest influence on the speed of the maturation process. We also contributed to the development of a general abstract framework for describing the catalytic cleavage processes of heteropolymers.

Relevant publications

  • Müller, V.; Marée, 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. Proceedings of the Royal Society of London. Series B: Biological Sciences 2001, 268, 235–242, doi:10.1098/rspb.2000.1358.
  • Müller, V.; Vigueras-Gómez, J.F.; Bonhoeffer, S. Decelerating Decay of Latently Infected Cells during Prolonged Therapy for Human Immunodeficiency Virus Type 1 Infection. Journal of Virology 2002, 76, 8963–8965, doi:10.1128/jvi.76.17.8963-8965.2002.
  • Bonhoeffer, S.; Funk, G.A.; Günthard, H.F.; Fischer, M.; Müller, V. Glancing behind Virus Load Variation in HIV-1 Infection. Trends in Microbiology 2003, 11, 499–504, doi:10.1016/j.tim.2003.09.002.
  • Bretscher, M.T.; Althaus, C.L.; Müller, V.; Bonhoeffer, S. Recombination in HIV and the Evolution of Drug Resistance: For Better or for Worse? BioEssays 2004, 26, 180–188, doi:10.1002/bies.10386.
  • Bartha, I.; Simon, P.; Müller, V. Has HIV Evolved to Induce Immune Pathogenesis? Trends in Immunology 2008, 29, 322–328, doi:10.1016/j.it.2008.04.005.
  • Sadiq, S.K.; Könnyü, B.; Müller, V.; Coveney, P.V. Reaction Kinetics of Catalyzed Competitive Heteropolymer Cleavage. J. Phys. Chem. B 2011, 115, 11017–11027, doi:10.1021/jp206321b.
  • Könnyű, B.; Sadiq, S.K.; Turányi, T.; Hírmondó, R.; Müller, B.; Kräusslich, H.-G.; Coveney, P.V.; Müller, V. Gag-Pol Processing during HIV-1 Virion Maturation: A Systems Biology Approach. PLOS Computational Biology 2013, 9, e1003103, doi:10.1371/journal.pcbi.1003103.
  • Móréh, Á.; Szilágyi, A.; Scheuring, I.; Müller, V. Variable Effect of HIV Superinfection on Clinical Status: Insights From Mathematical Modeling. Front. Microbiol. 2018, 9, doi:10.3389/fmicb.2018.01634.

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