Topological mapping of antigenic sites on the Rift Valley fever virus envelope glycoproteins using monoclonal antibodies

Abstract

A panel of 17 monoclonal antibodies (MAbs) to the G1 and G2 envelope glycoproteins of Rift Valley fever (RVF) virus were used to analyze the topography and functional properties of the viral antigenic sites. Four heterogeneous antigenic regions which may be interlinked were identified on the G1 protein and four distinct domains on the G2 protein by competitive binding assays. Comparison of the biological activities and epitope specificities of the MAbs against G1 showed that the antigenic domains I, II, and IV were involved in virus neutralization and haemagglutination at different potencies. For both the G1 and G2 proteins, determinants mapping to domain G1 Ia and G2 Ia were associated with very strong neutralization independent of complement (C'), suggesting that they represent biologically important areas. Domain G2 II was involved in haemagglutination and weak C' dependent neutralization while the other two G2 regions had no haemagglutination function and neutralized to a low level only in the presence of C'. Epitopes Ia and IIb on G1 and Ia and IIa on G2 were also associated with protection of mice against virulent RVFV infection, indicating that both envelope glycoproteins play an important role in RVF viral infection and pathogenesis.

Performance of Various Commercial Assays for the Detection of Toscana Virus Antibodies

“…Moreover, the agreement of VNT and the commercial assays was interpreted as slight. It has been known that phleboviral neutralization is a complex phenomenon involving a number antigenic epitopes and even the majority of the exposed persons develop antibodies against linear epitopes of N protein, the immune response against viral glycoproteins, which affects virus neutralization in vitro, have been shown to display considerable variation (Besselaar andBlackburn 1991, Di Bonito et al 2002). Patients with TOSV-induced neurological disease have also been observed to develop a differential antibody response against denatured viral proteins (Di Bonito et al 2002).…”

Characterization of the Candiru Antigenic Complex (Bunyaviridae: Phlebovirus), a Highly Diverse and Reassorting Group of Viruses Affecting Humans in Tropical America

“…The M segment of phleboviruses encodes two glycoproteins: Gn and Gc, and a nonstructural protein, NSm (41). As with other bunyaviruses, the phlebovirus envelope glycoproteins are important for viral infection, pathogenesis and immunity; they serve as neutralizing and hemagglutinin-inhibiting antibody targets and are exposed to selective pressure (3,6,30,46). Neutralizing epitopes typically depend on the tertiary structure of proteins, and even a single amino acid substitution may influence biological activity (24,53).…”

Phylogenetic relationships among members of the genus Phlebovirus (Bunyaviridae) based on partial M segment sequence analyses

“…As with other members of the Bunyaviridae, the phlebovirus envelope glycoproteins are important for viral infection, pathogenesis and immunity; they serve as neutralizing and haemagglutinin-inhibiting antibody targets (Keegan & Collett, 1986;Battles & Dalrymple, 1988;Pifat et al, 1988;Besselaar & Blackburn, 1991). In general, neutralizing epitopes depend on the tertiary structure of proteins and even a single amino acid substitution may be important for biological activity (Schmaljohn et al, 1990;Horling & Lundkvist, 1997).…”