West Nile virus envelope proteins: nucleotide sequence analysis of strains differing in mouse neuroinvasiveness

TJ Chambers, M Halevy… - Journal of General …, 1998 - microbiologyresearch.org
TJ Chambers, M Halevy, A Nestorowicz, CM Rice, S Lustig
Journal of General Virology, 1998microbiologyresearch.org
Several neuroinvasive and non-neuroinvasive West Nile (WN) viruses were characterized
by nucleotide sequencing of their envelope (E) protein regions. Prolonged passage in
mosquito cells caused loss of neuroinvasiveness and acquisition of an N-linked
glycosylation site, which is utilized. Limited passage in cell culture also caused glycosylation
but not attenuation, suggesting that glycosylation may not be directly responsible for
attenuation and that a second mutation (L68→ P) may also be involved. A monoclonal …
Several neuroinvasive and non-neuroinvasive West Nile (WN) viruses were characterized by nucleotide sequencing of their envelope (E) protein regions. Prolonged passage in mosquito cells caused loss of neuroinvasiveness and acquisition of an N-linked glycosylation site, which is utilized. Limited passage in cell culture also caused glycosylation but not attenuation, suggesting that glycosylation may not be directly responsible for attenuation and that a second mutation (L68 → P) may also be involved. A monoclonal antibody-neutralization escape mutant with a substitution at residue 307, a site common to other flavivirus escape mutants, was also attenuated. A partially neuroinvasive revertant regained the parental E sequence, implying that determinants outside of the E region may also influence attenuation. Data suggest that the neuroinvasive determinants may be similar to those for other flaviviruses. Also, sequence comparison with the WN virus (Nigeria) strain revealed considerable divergence of the E protein at the nucleotide and amino acid levels.
Microbiology Research