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California serogroup Gc (G1) glycoprotein is the principal determinant of pH-dependent cell fusion and entry
Journal article   Open access   Peer reviewed

California serogroup Gc (G1) glycoprotein is the principal determinant of pH-dependent cell fusion and entry

Matthew L Plassmeyer, Samantha S Soldan, Karen M Stachelek, Julio Martín-García and Francisco González-Scarano
Virology (New York, N.Y.), v 338(1)
20 Jul 2005
DOI: https://doi.org/10.1016/j.virol.2005.04.026
PMID: 15923017
Featured in Collection :   UN Sustainable Development Goals @ Drexel
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https://doi.org/10.1016/j.virol.2005.04.026View
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Abstract

Humans Virulence Leukemia Virus, Murine - genetics La Crosse virus - genetics Encephalitis Virus, California - genetics Encephalitis Virus, California - classification Encephalitis Virus, California - pathogenicity Cell Fusion Transfection Genes, Viral Viral Proteins - physiology Recombinant Proteins - metabolism Cell Line Cricetinae Gene Expression Transduction, Genetic Viral Proteins - chemistry Models, Molecular Recombinant Proteins - chemistry Viral Proteins - genetics Recombinant Proteins - genetics Quail Animals La Crosse virus - pathogenicity La Crosse virus - classification Protein Conformation Hydrogen-Ion Concentration
Members of the California serogroup of orthobunyaviruses, particularly La Crosse (LAC) and Tahyna (TAH) viruses, are significant human pathogens in areas where their mosquito vectors are endemic. Previous studies using wild-type LAC and TAH181/57, a highly neurovirulent strain with low neuroinvasiveness (Janssen, R., Gonzalez-Scarano, F., Nathanson, N., 1984. Mechanisms of bunyavirus virulence. Comparative pathogenesis of a virulent strain of La Crosse and an avirulent strain of Tahyna virus. Lab. Invest. 50 (4), 447-455), have demonstrated that the neuroinvasive phenotype maps to the M segment, the segment that encodes the two viral glycoproteins Gn (G2) and Gc (G1), as well as a non-structural protein NSm. To further define the role of Gn and Gc in fusion and entry, we prepared a panel of recombinant M segment constructs using LAC, TAH181/57, and V22F, a monoclonal-resistant variant of LAC with deficient fusion function. These M segment constructs were then tested in two surrogate assays for virus entry: a cell-to-cell fusion assay based on T7-luciferase expression, and a pseudotype transduction assay based on the incorporation of the bunyavirus glycoproteins on an MLV backbone. Both assays demonstrated that Gc is the principal determinant of virus fusion and cell entry, and furthermore that the region delineated by amino acids 860-1442, corresponding to the membrane proximal two-thirds of Gc, is key to these processes. These results, coupled with structural modeling suggesting homologies between the carboxy region of Gc and Sindbis virus E1, suggest that the LAC Gc functions as a type II fusion protein.

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