Structure-function analysis of two variants of mumps virus hemagglutinin-neuraminidase protein.
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.
Santos-López
Gerardo
G
Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Metepec, Puebla, México. gerardo.santos.lopez@gmail.com
Scior
Thomas
T
Borraz-Argüello
María del Tránsito
Mdel T
Vallejo-Ruiz
Verónica
V
Herrera-Camacho
Irma
I
Tapia-Ramírez
José
J
Reyes-Leyva
Julio
J
D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D014644:Genetic Variation / Q000235:genetics* / Q000276:immunology; D015707:HN Protein / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D009108:Mumps Vaccine / Q000737:chemistry / Q000235:genetics*; D009109:Mumps virus / Q000235:genetics* / Q000276:immunology; D017354:Point Mutation; D013329:Structure-Activity Relationship; D014709:Vero Cells
D015707:HN Protein; D009108:Mumps Vaccine