Structure-function analysis of two variants of mumps virus hemagglutinin-neuraminidase protein
Braz. j. infect. dis
;
13(1): 24-34, Feb. 2009. ilus, graf, tab
Article
Dans Anglais
| LILACS
| ID: lil-517811
ABSTRACT
A point mutation from guanine (G) to adenine (A) at nucleotide position 1081 in the hemagglutinin-neuraminidase (HN) gene has been associated with neurovirulence of Urabe AM9 mumps virus vaccine. This mutation corresponds to a glutamic acid (E) to lysine (K) change at position 335 in the HN glycoprotein. We have experimentally demonstrated that two variants of Urabe AM9 strain (HN-A1081 and HN-G1081) differ in neurotropism, sialic acidbinding affinity and neuraminidase activity. In the present study, we performed a structure-function analysis of that amino acid substitution; the structures of HN protein of both Urabe AM9 strain variants were predicted. Based on our analysis, the E/K mutation changes the protein surface properties and to a lesser extent their conformations, which in turn reflects in activity changes. Our modeling results suggest that this E/K interchange does not affect the structure of the sialic acid binding motif; however, the electrostatic surface differs drastically due to an exposed short alpha helix. Consequently, this mutation may affect the accessibility of HN to substrates and membrane receptors of the host cells. Our findings appear to explain the observed differences in neurotropism of these vaccine strains.
Texte intégral:
Disponible
Indice:
LILAS (Amériques)
Sujet Principal:
Variation génétique
/
Vaccin antiourlien
/
Protéine HN
/
Virus des oreillons
Type d'étude:
Étude pronostique
Limites du sujet:
Animaux
/
Humains
langue:
Anglais
Texte intégral:
Braz. j. infect. dis
Thème du journal:
Maladies transmissibles
Année:
2009
Type:
Article
/
descriptif de projet
Pays d'affiliation:
Mexique
Institution/Pays d'affiliation:
Facultad de Ciencias Químicas/MX
/
Instituto Mexicano del Seguro Social/MX
/
Instituto Politécnico Nacional/MX
/
Universidad Autónoma de Puebla/MX
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