Journal article
Mutagenesis of the La crosse virus glycoprotein supports a role for Gc (1066-1087) as the fusion peptide
Journal of neurovirology, Vol.12, pp.76-76
01 May 2006
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 used a panel of recombinant M segment constructs to demonstrate that a region corresponding to 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). These data suggested that the LACV Gc, like the alphavirus E1 and flavivirus E, functions as a type II fusion protein. Within the region 970-1350, a 22 amino acid hydrophobic segment (1066-1087) is predicted to correlate structurally with the fusion peptides of type 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 with cell-to-cell fusion and pseudotype transduction assays. 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. A mutation at position 1066 (W1066A) was particularly informative, since it did not affect glycoprotein expression, yet abolished fusion and entry. These results, coupled with the computational modeling, suggest that the LACV Gc functions as a type 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
- S SoldanM PlassmeyerK StachelekS RothJ Martin-GarciaF Gonzalez-Scarano
- Publication Details
- Journal of neurovirology, Vol.12, pp.76-76
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Identifiers
- 991019170499004721