Aproximaciones a la obtención de cápsidas más estables del virus de la fiebre aftosa y estudio de la generación de mutaciones compensatorias

• Autores: Eva Luna García
• Directores de la Tesis: Mauricio García Mateu (dir. tes.)
• Lectura: En la Universidad Autónoma de Madrid ( España ) en 2010
• Idioma: español
• Tribunal Calificador de la Tesis: Enrique Tabares López (presid.), Juan Carlos Saíz Calahorra (secret.), Miguel Ángel Martín Acebes (voc.), Francisco Sobrino Castelló (voc.), Miguel Ángel Martínez Sierra (voc.), C. López Galíndez (voc.), Francisco Rodríguez Aguirre (voc.)
• Materias:
  • Ciencias de la vida
    • Biología molecular
• Enlaces
  • Tesis en acceso abierto en: Biblos-e Archivo
• Resumen

  • Our laboratory is studying the molecular determinants of assembly, disassembly and stability of viral particles. As one model we are using foot-and-mouth-disease virus (FMDV), an economically important picornavirus for which much structural and functional information is available.

    The first part of this Ph.D. study was aimed at the generation of thermostable, but infectious and genetically stable FMDV mutants, either by isolation from viral populations or through rational protein engineering approaches. Such variants, if they could be obtained and characterized, would help to provide insights into the molecular basis of virus stability and its relationship with biological fitness, and could also facilitate the development of improved, thermostable FMD vaccines.

    In collaboration with Dr. Mateo from our laboratory, we have investigated the presence in a wide range of FMDV populations of virus variants with an increased resistance to thermal inactivation. The results with both uncloned and cloned populations, from three different serotypes, recovered from cytolytic or persistent infections, and/or subjected to either very few passages or extensive passaging in cell culture do not rule out the possibility that thermostable variants could be present in some specific FMDV populations. However, they clearly indicate that the presence of thermostable virus variants, even in small proportions, is not a general feature of FMDV quasispecies. This suggests that no substantial increase in the stability of FMDV against thermal inactivation may readily occur without a negative effect on viral function