A mutation in the envelope protein fusion loop attenuates mouse neuroinvasiveness of the NY99 strain of West Nile virus

Shuliu Zhang; Li Li; Sara E. Woodson; Claire Y.H. Huang; Richard M. Kinney; Alan D.T. Barrett; David W.C. Beasley

doi:10.1016/j.virol.2006.05.025

A mutation in the envelope protein fusion loop attenuates mouse neuroinvasiveness of the NY99 strain of West Nile virus

Shuliu Zhang, Li Li, Sara E. Woodson, Claire Y.H. Huang, Richard M. Kinney, Alan D.T. Barrett, David W.C. Beasley

Research output: Contribution to journal › Article › peer-review

38 Scopus citations

Abstract

Substitutions were engineered individually and in combinations at the fusion loop, receptor-binding domain and a stem-helix structure of the envelope protein of a West Nile virus strain, NY99, and their effects on mouse virulence and presentation of epitopes recognized by monoclonal antibodies (MAbs) were assessed. A single substitution within the fusion loop (L107F) attenuated mouse neuroinvasiveness of NY99. No substitutions attenuated NY99 neurovirulence. The L107F mutation also abolished binding of a non-neutralizing MAb, 3D9, whose epitope had not been previously identified. MAb 3D9 was subsequently shown to be broadly cross-reactive with other flaviviruses, consistent with binding near the highly conserved fusion loop.

Original language	English (US)
Pages (from-to)	35-40
Number of pages	6
Journal	Virology
Volume	353
Issue number	1
DOIs	https://doi.org/10.1016/j.virol.2006.05.025
State	Published - Sep 15 2006

Keywords

Envelope protein
Epitope
Flavivirus vaccine
Fusion loop
Infectious clone
Mutagenesis
Neuroinvasiveness
Neurovirulence
Pathogenesis
West Nile virus

ASJC Scopus subject areas

Virology

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10.1016/j.virol.2006.05.025

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title = "A mutation in the envelope protein fusion loop attenuates mouse neuroinvasiveness of the NY99 strain of West Nile virus",

abstract = "Substitutions were engineered individually and in combinations at the fusion loop, receptor-binding domain and a stem-helix structure of the envelope protein of a West Nile virus strain, NY99, and their effects on mouse virulence and presentation of epitopes recognized by monoclonal antibodies (MAbs) were assessed. A single substitution within the fusion loop (L107F) attenuated mouse neuroinvasiveness of NY99. No substitutions attenuated NY99 neurovirulence. The L107F mutation also abolished binding of a non-neutralizing MAb, 3D9, whose epitope had not been previously identified. MAb 3D9 was subsequently shown to be broadly cross-reactive with other flaviviruses, consistent with binding near the highly conserved fusion loop.",

keywords = "Envelope protein, Epitope, Flavivirus vaccine, Fusion loop, Infectious clone, Mutagenesis, Neuroinvasiveness, Neurovirulence, Pathogenesis, West Nile virus",

author = "Shuliu Zhang and Li Li and Woodson, {Sara E.} and Huang, {Claire Y.H.} and Kinney, {Richard M.} and Barrett, {Alan D.T.} and Beasley, {David W.C.}",

note = "Funding Information: This study was supported in part by grants from the Clayton Foundation for Research (to ADTB) and NIH (AI063468 to DWCB). DWCB was supported in part by the James W. McLaughlin Fellowship Fund. We also thank Dr. Bob Tesh and Hilda Guzman for generously providing inactivated viral antigens used for hemagglutination inhibition testing and Dr. Steve Higgs for MAb 4G2.",

year = "2006",

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doi = "10.1016/j.virol.2006.05.025",

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AU - Zhang, Shuliu

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AU - Woodson, Sara E.

AU - Huang, Claire Y.H.

AU - Kinney, Richard M.

AU - Barrett, Alan D.T.

AU - Beasley, David W.C.

N1 - Funding Information: This study was supported in part by grants from the Clayton Foundation for Research (to ADTB) and NIH (AI063468 to DWCB). DWCB was supported in part by the James W. McLaughlin Fellowship Fund. We also thank Dr. Bob Tesh and Hilda Guzman for generously providing inactivated viral antigens used for hemagglutination inhibition testing and Dr. Steve Higgs for MAb 4G2.

PY - 2006/9/15

Y1 - 2006/9/15

N2 - Substitutions were engineered individually and in combinations at the fusion loop, receptor-binding domain and a stem-helix structure of the envelope protein of a West Nile virus strain, NY99, and their effects on mouse virulence and presentation of epitopes recognized by monoclonal antibodies (MAbs) were assessed. A single substitution within the fusion loop (L107F) attenuated mouse neuroinvasiveness of NY99. No substitutions attenuated NY99 neurovirulence. The L107F mutation also abolished binding of a non-neutralizing MAb, 3D9, whose epitope had not been previously identified. MAb 3D9 was subsequently shown to be broadly cross-reactive with other flaviviruses, consistent with binding near the highly conserved fusion loop.

AB - Substitutions were engineered individually and in combinations at the fusion loop, receptor-binding domain and a stem-helix structure of the envelope protein of a West Nile virus strain, NY99, and their effects on mouse virulence and presentation of epitopes recognized by monoclonal antibodies (MAbs) were assessed. A single substitution within the fusion loop (L107F) attenuated mouse neuroinvasiveness of NY99. No substitutions attenuated NY99 neurovirulence. The L107F mutation also abolished binding of a non-neutralizing MAb, 3D9, whose epitope had not been previously identified. MAb 3D9 was subsequently shown to be broadly cross-reactive with other flaviviruses, consistent with binding near the highly conserved fusion loop.

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KW - Epitope

KW - Flavivirus vaccine

KW - Fusion loop

KW - Infectious clone

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KW - Neuroinvasiveness

KW - Neurovirulence

KW - Pathogenesis

KW - West Nile virus

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A mutation in the envelope protein fusion loop attenuates mouse neuroinvasiveness of the NY99 strain of West Nile virus

Abstract

Keywords

ASJC Scopus subject areas

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