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Determinantes estructurales para que la hemaglutinina H5N1 que evoluciona naturalmente cambie su especificidad de
Kannan Tharakaraman1, Rahul Raman, Karthik Viswanathan
1Department of Biological Engineering, Koch Institute of Integrative Cancer Research, Infectious Diseases Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Cell
|June 11, 2013
Resumen
Comprender la transmisión de la gripe aviar H5N1 es clave. Mutaciones específicas en la hemaglutinina.
Área de la Ciencia:
- Virología Virología.
- Biología Estructural Biología estructural.
- Biología Molecular Biología Molecular
Sus antecedentes:
- La transmisión de humano a humano del virus de la influenza aviar A altamente patógena (H5N1) es una preocupación significativa para la salud pública.
- La adaptación viral a los receptores del tracto respiratorio humano, específicamente a los receptores glicanos humanos, es un factor crítico para una transmisión eficiente.
Objetivo del estudio:
- Definir las características estructurales del sitio de unión al receptor de la hemaglutinina (HA) H5 (RBS) necesarias para cambiar la preferencia de unión de los receptores de glicano aviar a los humanos.
- Identificar las mutaciones que confieren unión al receptor humano y evaluar su potencial para la adaptación humana al H5N1.
Principales métodos:
- Análisis estructural de los sitios de unión a los receptores H5 HA.
- Estudios de mutagenesis para alterar las propiedades de unión al receptor de HA.
- Evaluación de la unión viral a los receptores de glicano aviar y humano.
Principales resultados:
- Se estableció un marco estructural para las mutaciones H5 HA que permite un cambio cuantitativo a la unión al receptor humano.
- Las mutaciones previamente identificadas que confieren transmisión por aerosol en cepas H5N1 más antiguas no indujeron un cambio cuantitativo en las cepas H5N1 actualmente en circulación.
- Los HAs de los clados H5N1 circulantes pueden lograr un cambio cuantitativo a los receptores humanos con tan solo una mutación de un par de bases.
Conclusiones:
- El estudio identifica las características críticas de H5 HA RBS requeridas para la adaptación del receptor humano.
- Los hallazgos destacan que las mutaciones que confieren la unión al receptor humano pueden variar entre los clados H5N1.
- Las mutaciones identificadas sirven como marcadores potenciales para el monitoreo de cepas H5N1 con potencial pandémico.
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