Epitope Mapping Studies with Neutralizing and Non-neutralizing Monoclonal Antibodies to the G1 and G2 Envelope Glycoproteins of Hantaan Virus

Wang, M.; Pennock, David G.; Spik, Kristin; Schmaljohn, Connie S.

doi:10.1006/viro.1993.1652

Cited by 48 publications

(41 citation statements)

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“…This defined epitope is also in line with the region of DNA segment from aa 399-565 that induced the neutralizing antibody responses to SNV [Bharadwaj et al, 1999]. Non-neutralization epitopes have been mapped to the N-terminal third of the G1 protein of hantaan virus [Wang et al, 1993], however, the evidences described above indicated that the C-terminal third of G1 protein constitute one of major neutralization epitopes of hantaviruses and may contribute to bind the virus receptor on infected cells and related to virus virulence.…”

Section: Discussionsupporting

confidence: 52%

“…This epitope is close to a site (aa 415) where a neutralizing mouse Mab (16D2) was mapped by using antibody-escape mutants [Wang et al, 1993]. It is also near a site identified in an attenuated HTNV mutant (mu11E10, aa 515), which was postulated to be related to virulence in mice [Ebihara et al, 2000].…”

Section: Discussionmentioning

confidence: 94%

“…A competitive binding study of 24 mouse monoclonal antibodies (Mabs) revealed at least nine distinct, partially overlapping antigenic sites on HTNV G1 and G2 [Arikawa et al, 1989]. In subsequent studies with the same Mabs, sequence analysis of the genomes of Mab escape mutants revealed that noncontiguous amino acids form neutralizing epitopes (i.e., conformational epitopes) on the envelope proteins [Wang et al, 1993;Kikuchi et al, 1998]. Conformational, neutralizing epitopes were also identified on PUUV using phage display to express random peptides and by reacting the expression products with two G2-specific Mabs to PUUV [Salonen et al, 1998, Heiskanen et al, 1999, Nicacio et al, 2000.…”

Section: Introductionmentioning

confidence: 99%

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Generation of an HFRS patient‐derived neutralizing recombinant antibody to Hantaan virus G1 protein and definition of the neutralizing domain

Liang¹,

Mähler

Koch

et al. 2002

Journal of Medical Virology

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Hantaan virus (HTNV) in the Hantavirus genus, family Bunyaviridae, is the major cause of severe hemorrhagic fever with renal syndrome (HFRS). We prepared a combinatorial phage display library of human Fabs to HTNV from RNA extracted from the blood lymphocytes of a convalescent HFRS patient. We selected two G1 glycoproteinspecific clones and one nucleocapsid protein (N)-specific clone from the Fab library for further studies. The human Fab antibodies were converted to IgG form in baculovirus/insect cells system by using cassette vectors that we developed earlier. Characterization of the recombinant antibodies revealed that the two G1-specific IgGs, could bind to and neutralize HTNV but not Seoul virus (SEOV). The N-specific IgG did not neutralize either HTNV or SEOV. Sequence analysis revealed that the two G1-specific clones differed by only one predicted amino acid in their complementarity determining regions, CDR3. Epitope mapping studies were carried out with one of the two G1-specific clones and synthetic peptides representing portions of HTNV G1. Results indicated that the recombinant antibody recognizes the core amino acid sequence LTKTLVIGQ, which is found near the C-terminus of HTNV G1. These results are the first to define a neutralizing epitope on the G1 protein of HTNV using an antibody derived from an HFRS patient.

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Section: Discussionsupporting

confidence: 52%

Section: Discussionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

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Generation of an HFRS patient‐derived neutralizing recombinant antibody to Hantaan virus G1 protein and definition of the neutralizing domain

Liang¹,

Mähler

Koch

et al. 2002

Journal of Medical Virology

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“…An additional possible consequence of this finding could be apparent if vaccine development is contemplated for FCV. In general, antibodies directed against the glycoprotein antigens of hantaviruses are neutralizing (Arikawa et al, 1989(Arikawa et al, , 1992Chu et al, 1994;Lundkvist & Niklasson, 1992;Wang et al, 1993a;Yoshimatsu et al, 1992). While antibodies against the G1 epitope identified previously are not known to be neutralizing, its immunodominance in vivo and conservation across a significant portion of the range of P. maniculatus makes it a promising target for further study.…”

Section: Discussionmentioning

confidence: 99%

Dominant Glycoprotein Epitope of Four Corners Hantavirus is Conserved Across a Wide Geographical Area

Hjelle

Chavez-Giles²,

Torrez‐Martinez³

et al. 1994

Journal of General Virology

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A newly identified hantavirus, tentatively called Four Corners virus (FCV), was found to be the aetiological agent of a 1993 outbreak of hantavirus pulmonary syndrome (HPS) in the southwestern United States. Immunodominant epitopes of 43 and 31 amino acids were identified in the nucleocapsid protein and G1 glycoprotein, respectively. The G1 genes of different hantaviruses are highly divergent, suggesting that geographically diverse FCVs might fail to cross-react owing to antigenic drift. We now show that the immunodominant epitope of G1 is conserved among 18 FCVs from a broad geographical area, despite extensive nucleotide sequence heterogeneity. Antibodies from all 45 HPS patients, separated by more than 3000 km were shown to be reactive with the dominant G1 epitope. Evidence for limited cross-reactivity between the G1 antigen of a novel hantavirus of the cotton rat and that of FCV is presented.

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“…HR can also cause antigenic shift, which is important for the emergence of new viral pathogens (6,27). Here, HR is found in the M segment, which encodes the protective epitopes of the virus in G1 and G2 (25). G1 is also an important virulence determinant (18).Through HR, lineage I has acquired nearly complete G1 from lineage III.…”

mentioning

confidence: 99%

Discovery of Severe Fever with Thrombocytopenia Syndrome Bunyavirus Strains Originating from Intragenic Recombination

Ding

2012

J Virol

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This study analyzes available severe fever with thrombocytopenia syndrome virus (SFTSV) genomes and reports that a sublineage of lineage I bears a unique M segment recombined from two of three prevailing SFTSV lineages. Through recombination, the sublineage has acquired nearly complete G1 associated with protective epitopes from lineage III, suggesting that this recombination has the capacity to induce antigenic shift of the virus. Therefore, this study provides some valuable implications for the vaccine design of SFTSV.

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Epitope Mapping Studies with Neutralizing and Non-neutralizing Monoclonal Antibodies to the G1 and G2 Envelope Glycoproteins of Hantaan Virus

Cited by 48 publications

References 0 publications

Generation of an HFRS patient‐derived neutralizing recombinant antibody to Hantaan virus G1 protein and definition of the neutralizing domain

Generation of an HFRS patient‐derived neutralizing recombinant antibody to Hantaan virus G1 protein and definition of the neutralizing domain

Dominant Glycoprotein Epitope of Four Corners Hantavirus is Conserved Across a Wide Geographical Area

Discovery of Severe Fever with Thrombocytopenia Syndrome Bunyavirus Strains Originating from Intragenic Recombination

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