Journal article
Mutagenesis of the La Crosse Virus glycoprotein supports a role for Gc (1066–1087) as the fusion peptide
Virology (New York, N.Y.), v 358(2), pp 273-282
2007
PMID: 17027056
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Abstract
The La Crosse Virus (LACV) M segment encodes two glycoproteins (Gn and Gc), and plays a critical role in the neuropathogenesis of LACV infection as the primary determinant of neuroinvasion. A recent study from our group demonstrated that the region comprising the membrane proximal two-thirds of Gc, amino acids 860–1442, is critical in mediating LACV fusion and entry. Furthermore, computational analysis identified structural similarities between a portion of this region, amino acids 970–1350, and the E1 fusion protein of two alphaviruses: Sindbis virus and Semliki Forrest virus (SFV). Within the region 970–1350, a 22-amino-acid hydrophobic segment (1066–1087) is predicted to correlate structurally with the fusion peptides of class II fusion proteins. We performed site-directed mutagenesis of key amino acids in this 22-amino acid segment and determined the functional consequences of these mutations on fusion and entry. Several mutations within this hydrophobic domain affected glycoprotein expression to some extent, but all mutations either shifted the pH threshold of fusion below that of the wild-type protein, reduced fusion efficiency, or abrogated cell-to-cell fusion and pseudotype entry altogether. These results, coupled with the aforementioned computational modeling, suggest that the LACV Gc functions as a class II fusion protein and support a role for the region Gc 1066–1087 as a fusion peptide.
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Details
- Title
- Mutagenesis of the La Crosse Virus glycoprotein supports a role for Gc (1066–1087) as the fusion peptide
- Creators
- Matthew L Plassmeyer - Department of Neurology, 3 West Gates, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104-4283, USASamantha S Soldan - Department of Neurology, 3 West Gates, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104-4283, USAKaren M Stachelek - Department of Neurology, 3 West Gates, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104-4283, USASusan M Roth - Graduate Group Molecular and Cell Biology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104-6058, USAJulio Martín-García - Department of Neurology, 3 West Gates, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104-4283, USAFrancisco González-Scarano - Department of Neurology, 3 West Gates, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104-4283, USA
- Publication Details
- Virology (New York, N.Y.), v 358(2), pp 273-282
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:000244272500004
- Scopus ID
- 2-s2.0-33846526211
- Other Identifier
- 991014878007704721
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- Web of Science research areas
- Virology