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Abstract

Quantifying the early steps of viral infection in cells is a new area of physical virology. It is dedicated to the analysis of the main pathways used by viruses for reproduction. Most viruses entering cells after binding to specific membrane receptors are enveloped in an endosomal compartment (Fig. 9.1) (see Whittaker et al. 2000; Greber and Way 2006). These viruses entering through the endosome have to escape this compartment later on. Enveloped viruses, such as influenza, contain membrane-associated glycoproteins, which mediate the fusion between the viral and endosomal membranes, from which they have to escape. In particular, acidification of the endosome triggers the conformational change of the influenza hemagglutinins, leading to endosome-virus membranes fusion and release of genes into the cytoplasm. Following the endosomal escape, nuclear replication viruses have to travel through the crowded cytoplasm to reach replication sites such as the nucleus to deliver their genetic material through the nuclear pores. Virus motion into the cytoplasm is composed of periods described as Brownian, while others are directed motion along microtubules. While the cytoplasmic movement of viral particles towards the nucleus is facilitated by the microtubular network and viral proteins, very little is known about the fate of non-viral DNA vectors in the cytoplasm.

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Bibliography

  • A. Ajdari, Europhys. Lett. 31, 69 (1995).

    Google Scholar 

  • Amoruso, C., T. Lagache, and D. Holcman (2011), “Modeling the early steps of cytoplasmic trafficking in viral infection and gene delivery,” SIAM. J. Appl. Math. 71 (6), pp.2334–2358.

    Google Scholar 

  • D. Coy, M. Vagenbach and J.J. Howard, Biol. Chem. 274, 3667 (1999).

    Google Scholar 

  • Dauty E. and A.S. Verkman (2005), “Actin cytoskeleton as the principal determinant of size-dependent DNA mobility in cytoplasm: a new barrier for non-viral gene delivery,” J. Biol. Chem. 280 pp.7823–7828.

    Google Scholar 

  • Farr, G.A., L.G. Zhang, and P. Tattersall (2005), “Parvoviral virions deploy a capsid-tethered lipolytic enzyme to breach the endosomal membrane during cell entry,” Proc. Natl. Acad. Sci. USA 102, pp.17148–17153.

    Google Scholar 

  • Garabedian, P.R. (1964), Partial Differential Equations, Wiley, NY.

    Google Scholar 

  • Greber, U.F. and M. Way (2006), “A superhighway to virus infection,” Cell 124 (4), pp.741–754.

    Google Scholar 

  • Holcman, D. and Z. Schuss (2004), “Escape through a small opening: receptor trafficking in a synaptic membrane,” J. Stat. Phys., 117 (5/6), 191–230.

    Google Scholar 

  • Holcman, D. (2007), “Modeling viral and DNA trafficking in the cytoplasm of a cell,” J. Stat. Phys. 127, pp.471–494.

    Google Scholar 

  • Huang, Q., R. Opitz, E.W. Knapp, A. Herrmann, “Protonation and stability of the globular domain of influenza virus hemagglutinin.” Biophys J., 82 (2), 1050–1058 (2002).

    Article  Google Scholar 

  • S. J. King and T. A Schroer, Dynactin Increases the Processivity of the Cytoplasmic Dynein Motor, Nat. Cell Biol., 2 (2000), pp. 20–24.

    Article  Google Scholar 

  • Knessl, C., M. Mangel, B.J. Matkowsky, and Z. Schuss (1984a), “Solution of Kramers-Moyal equations for problems in chemical physics,” J. Chem. Phys. 81, pp.1285–1293.

    Google Scholar 

  • Knessl, C., B.J. Matkowsky, Z. Schuss, and C. Tier (1984b), “An asymptotic theory of large deviations for Markov jump processes,” SIAM J. Appl. Math. 45, pp.1006–1102.

    Google Scholar 

  • Krumbiegel M., A. Herrmann, R. Blumenthal (1994) Kinetics of the low pH-induced conformational changes and fusogenic activity of influenza hemagglutinin. Biophys J 67:2355–2360.

    Article  Google Scholar 

  • Lagache, T. and D. Holcman (2008a), “Effective motion of a virus trafficking inside a biological cell,” SIAM. J. Appl. Math. 68, pp.1146–1167.

    Google Scholar 

  • Lagache, T. and D. Holcman (2008b), “Quantifying intermittent transport in cell cytoplasm,” Phys. Rev. E 77, 030901.

    Google Scholar 

  • Lagache, T., E. Dauty, and D. Holcman (2009a), “Physical principles and models describing intracellular virus particle dynamics,” Curr. Opin. Microbiol. 12 (4), pp.439–445.

    Google Scholar 

  • Lagache, T., E. Dauty, and D. Holcman (2009b), “Quantitative analysis of virus and plasmid trafficking in cells,” Phys. Rev. E, Stat. Nonlin. Soft Matter Phys. 79:011921

    Google Scholar 

  • Lagache, T., O. Danos, D. Holcman (2012), “Modeling the step of endosomal escape during cell infection by a nonenveloped virus,” Biophys. J. 102 (5), pp.980–989.

    Google Scholar 

  • Lagache, T., D. Holcman, pre-print (2015).

    Google Scholar 

  • R. Lipowsky, S. Klumpp and T.M. Nieuwenhuizen, Phys. Rev. Lett. 87, 108101 (2001).

    Google Scholar 

  • F. Nedelec, T. Surrey and A.C. Maggs, Phys Rev Lett. 86, 3192 (2001).

    Article  ADS  Google Scholar 

  • S. Ozawa, Proc. Japan. Acad. 56, 459 (1980).

    Article  MATH  Google Scholar 

  • Rachakonda, P.S., M. Veit, T. Korte, K. Ludwig, C. Böttcher, Q. Huang, M.F.G. Schmidt, and A. Herrmann (2007), “The relevance of salt bridges for the stability of the influenza virus hemagglutinin,” FASEB J. 21, pp.995–1002.

    Google Scholar 

  • S. Redner, A Guide to First Passage Processes, Cambridge University Press, Cambridge, Massachussets, 2001.

    Book  MATH  Google Scholar 

  • Lakadamyali M, M. J. Rust, X. Zhuang (2006) Ligands for clathrin-mediated endocytosis are differentially sorted into distinct populations of early endosomes. Cell 124: 997–1009.

    Article  Google Scholar 

  • Sakai et al. Dual wavelength imaging allows analysis of membrane fusion of influenza virus inside cells, J. of Virology. 4 2006.

    Google Scholar 

  • Schuss, Z., A. Singer, and D. Holcman (2007), “The narrow escape problem for diffusion in cellular microdomains,” Proc. Natl. Acad. Sci. USA, 104, 16098–16103.

    Google Scholar 

  • Schuss, Z. (2010b), Theory and Applications of Stochastic Processes, and Analytical Approach, Springer series on Applied Mathematical Sciences 170, NY.

    Google Scholar 

  • Seisenberger, G., M.U. Ried, T. Endress, H. Brüning, M. Hallek, Bräuchle (2001), “Real-time single-molecule imaging of the infection pathway of an adeno-associated virus,” Science 294 (5548), pp.1929–1932.

    Google Scholar 

  • G.A. Smith et al., Proc. Natl. Acad. Sci. U.S.A. 45, 16034 (2004).

    Google Scholar 

  • Sodeik, B. (2000), “Mechanisms of viral transport in the cytoplasm,” Trends Microbiol. 8 pp.465–472.

    Google Scholar 

  • Whittaker, G.R., M. Kann, A. Helenius (2000), “Viral entry into the nucleus,” Annu. Rev. Cell Dev. Biol. 16, pp.627–651.

    Google Scholar 

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Holcman, D., Schuss, Z. (2015). Modeling the Early Steps of Viral Infection in Cells. In: Stochastic Narrow Escape in Molecular and Cellular Biology. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-3103-3_9

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