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
Artigo
em Inglês
| LILACS
| ID: lil-517811
Biblioteca responsável:
BR1.1
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.
Texto completo:
Disponível
Coleções:
Bases de dados internacionais
Contexto em Saúde:
Agenda de Saúde Sustentável para as Américas
Problema de saúde:
Objetivo 5 Medicamentos, vacinas e tecnologias sanitárias
Base de dados:
LILACS
Assunto principal:
Variação Genética
/
Vacina contra Caxumba
/
Proteína HN
/
Vírus da Caxumba
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
/
Humanos
Idioma:
Inglês
Revista:
Braz. j. infect. dis
Assunto da revista:
Doenças Transmissíveis
Ano de publicação:
2009
Tipo de documento:
Artigo
/
Documento de projeto
País de afiliação:
México
Instituição/País de afiliação:
Facultad de Ciencias Químicas/MX
/
Instituto Mexicano del Seguro Social/MX
/
Instituto Politécnico Nacional/MX
/
Universidad Autónoma de Puebla/MX