Amino acid change 335 E to K affects the sialic-acid-binding and neuraminidase activities of Urabe AM9 mumps virus hemagglutinin-neuraminidase glycoprotein.
A mutation coding for the amino acid change E335 to K is frequently found in the hemagglutinin-neuraminidase (HN) gene of Urabe AM9 mumps viruses isolated during post-vaccination meningitis cases. To identify if this mutation modifies the biological activities of the HN glycoprotein, two variants of Urabe AM9 vaccine differing at amino acid 335 (HN-E335 and HN-K335) were isolated and their receptor-binding specificity was determined by means of competence assays. Pre-incubation of the viruses with sialic acids inhibited both syncytia formation in Vero cells and replication in SH-SY5Y cells. Thus, HN-K335 showed higher affinity towards sialylalpha2,6lactose, whereas HN-G335 preferred sialylalpha2,3lactose. These results are relevant because a high expression of sialylalpha2,6lactose in nerve cells was confirmed by means of Sambucus nigra lectin-cytochemistry. In addition, kinetics assays showed that HN-K335 and HN-E335 also differ in their hydrolysis rate (Vmax values of 37.5 vs. 3.5 nmol min-1mg-1, respectively). Therefore, HN-K335 variant presented a neuraminidase activity level 11-fold higher than that of HN-E335 variant. In conclusion, the mutation affects the receptor-binding and neuraminidase activities of Urabe AM9 mumps virus variants.
Reyes-Leyva
Julio
J
Laboratorio de Virología y Biología Molecular, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Mexico. jreyesleyva@correo.unam.mx
Baños
Rocío
R
Borraz-Argüello
María
M
Santos-López
Gerardo
G
Rosas
Nora
N
Alvarado
Gabriela
G
Herrera
Irma
I
Vallejo
Verónica
V
Tapia-Ramírez
José
J
D019943:Amino Acid Substitution; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D015707:HN Protein / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D009109:Mumps virus / Q000235:genetics / Q000502:physiology*; D020125:Mutation, Missense; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism*; D053585:Virus Attachment
D015707:HN Protein; D011991:Receptors, Virus; D019158:N-Acetylneuraminic Acid