Friday, 22nd September 2017

Virology and Microbiology

    Molecular bases of parvovirus pathogenesis and anti-cancer potential



José María Almendral







Research summary:



The research of the laboratory is focused in two partly overlapping issues: (A) the evolutionary dynamics of parvovirus in disease, and (B) the cell-host interactions underlying the oncotropism of these viruses. Both approaches are aimed at eventually designing safe anti-cancer biological tools. Our viral model is the parvovirus Minute Virus of Mice (MVM) in infections of normal and immunodeficient mice. Main specific topics being currently addressed are: (I) Pathogenesis and evolution: MVM populations associated with the development of a severe mouse hemopoietic disease are characterized by a high genetic heterogeneity localized at the capsid tropism determinant (Figure 1). Understanding the role of this domain in viral pathogenesis is a main target of our research. (II) Structure-Function analysis of the capsid: we are studying protein signals regulating the phosphorylation and intracellular traffic of trimeric assembly intermediates  (Figure 2) relating to the rational design of domains increasing viral maturation and oncotropism. (III) Anti-cancer features: we are undertaking a wide analysis of MVM interaction with human normal and transformed cells trying to identify potential cancer therapeutic targets involved in the regulation of MVM life cycle (Figure 3).


Selected Publications:

Maroto, B., Valle, N., Saffrich, R., and J. M. Almendral. (2004). Nuclear export of the non-envelopped MVM virion is directed by an unordered protein signal exposed on the capsid surface. J. Virol. 78, 10685-10694.

Lopez-Bueno, A., Segovia, J.C., Bueren, J.A., O´Sullivan, G., Tattersall, P., and J.M. Almendral. (2008).  Evolution to pathogenicity of the parvovirus MVM in immunodeficient mice involves genetic heterogeneity at the capsid domain that determines tropism. J.Virol. 82, 1195-1203.

Riolobos, L., Valle, N., Hernando, E., Maroto, B., Kann, M., and J. M. Almendral. Viral oncolysis that targets Raf-1 signalling control of nuclear transport. (2010). J. Virol., 84, 2090-2099.

Ventoso, I., Berlanga, J.J., and J. M. Almendral. (2010). Translational control by the Protein Kinase R restricts Minute Virus of Mice infection: role in parvovirus oncolysis.J. Virol., 84, 5043-5051.

Sánchez-Martínez, C, Grueso, E., Carroll, M., Rommelaere, J., and J. M. Almendral. (2012). Essential role of the unordered VP2 n-terminal domain of the parvovirus MVM capsid in nuclear assembly and endosomal enlargement of the virion fivefold channel for cell entry. Virology 432, 45-56.