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. 2010 Jul 20;403(1):85-91.
doi: 10.1016/j.virol.2010.03.038. Epub 2010 May 6.

Role of BC loop residues in structure, function and antigenicity of the West Nile virus envelope protein receptor-binding domain III

Shuliu Zhang  1 , Evgeniy I Bovshik, Rodrigo Maillard, Gregory D Gromowski, David E Volk, Catherine H Schein, Claire Y-H Huang, David G Gorenstein, James C Lee, Alan D T Barrett, David W C Beasley
Affiliations

Role of BC loop residues in structure, function and antigenicity of the West Nile virus envelope protein receptor-binding domain III

Shuliu Zhang et al. Virology. .

Abstract

Site-directed mutagenesis of residues in the BC loop (residues 329-333) of the envelope (E) protein domain III in a West Nile virus (WNV) infectious clone and in plasmids encoding recombinant WNV and dengue type 2 virus domain III proteins demonstrated a critical role for residues in this loop in the function and antigenicity of the E protein. This included a strict requirement for the tyrosine at residue 329 of WNV for virus viability and E domain III folding. The absence of an equivalent residue in this region of yellow fever group viruses and most tick-borne flavivirus suggests there is an evolutionary divergence in the molecular mechanisms of domain III folding employed by different flaviviruses.

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Figures

Figure 1
Figure 1
Location of BC loop (residues 329-333, in cyan) in the WNV E domain III: (a) lateral view of domain III, oriented as for the complete E protein structure (inset); (b) rotated 30° to the left to show the location of Y329 (in yellow). (c) Amino acid sequence alignment of flavivirus domain III residues equivalent to 302-337 of WNV; flavivirus-conserved cysteines and BC loop residues 329-333 are boxed. Mammalian tick-borne flaviviruses are ordered according to their proximity to the root of that branch in previous phylogenetic analyses of their evolution (Gaunt et al., 2001; Grard et al., 2007) showing replacement of tyrosine with phenylalanine and shortening of the BC loop.
Figure 2
Figure 2
Reactivity of anti-WNV MAbs 7H2, 5H10 and 5C5 with E proteins of WNV variants encoding domain III mutations in infected Vero cell lysate antigen preparations.
Figure 3
Figure 3
Comparative growth kinetics in Vero cells of wild-type (w.t.) WNV infectious clone and variants encoding substitutions at residues 330-333 of the envelope protein domain IIII. (Multiplicity of infection = 0.05 plaque forming unit/cell; error bars are 1 standard deviation.)
Figure 4
Figure 4
Effects of mutations at the conserved tyrosine present in mosquito-borne flavivirus E protein domain III on binding of (a) WNV-specific or (b) DENV-2-specific monoclonal antibodies to recombinant MBP-WNV or MBP-DENV-2 domain III fusion proteins, respectively, by ELISA.
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References

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