Analysis of linear epitopes recognised by the primary human antibody response to a variable region of the attachment (G) protein of respiratory syncytial virus

Cane, Patricia A.

doi:10.1002/(sici)1096-9071(199704)51:4<297::aid-jmv7>3.0.co;2-0

Cited by 75 publications

(66 citation statements)

References 23 publications

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“…For HRSV group A, it has been documented that amino acid changes in the C-terminal third of the G protein are often associated with the loss of antigenic epitopes in both natural strains and antibody escape mutants (4,11,15,24,27,36,40,54). These changes coincide to some extent with sites described as being under positive selection (7,43,71,74).…”

Section: Discussionmentioning

confidence: 99%

Ten Years of Global Evolution of the Human Respiratory Syncytial Virus BA Genotype with a 60-Nucleotide Duplication in the G Protein Gene

Trento

Casas

Calderón

et al. 2010

J Virol

167

207

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Human respiratory syncytial virus (HRSV), a member of the Pneumovirus genus within the Paramyxoviridae family, is recognized as the leading agent responsible for severe respiratory infections in the pediatric population (31, 34, 35) and a pathogen of considerable importance in vulnerable adults (23,24). The global respiratory syncytial virus (RSV) disease burden is estimated at 64 million cases and 160,000 deaths every year (70). This virus causes regular seasonal epidemics which take place during the winter months in temperate countries or during the rainy season in tropical areas (12). A peculiar aspect of HRSV is that the immune response produced by infection does not confer long-lasting protection, which is why reinfections are common throughout life (30).Neutralization tests performed with hyperimmune serum (16) and reactivity with specific monoclonal antibodies (4, 45) were used to classify HRSV isolates into two antigenic groups, A and B, which correlated with genetically distinct viruses (18). The main differences between these two groups are located in the major attachment G protein. This protein is a type II glycoprotein that shares neither sequence nor structural features with the attachment proteins (HN or H) of other paramyxoviruses (69), and it represents one of the targets of the immune response (27, 43). The full-length membranebound G protein (Gm) of 292 to 319 amino acids (depending on the viral strain) is also expressed in a secreted version (Gs) that lacks the transmembrane domain due to alternative initiation of translation at a second in-frame AUG codon in the G open reading frame (M48) (52). The G protein is the viral gene product with the highest degree of antigenic and genetic diversity among viral isolates (4,18,28,45). Most changes are concentrated in two hypervariable regions that flank a highly conserved central region of the G protein ectodomain, which includes a cluster of four cysteines and the putative receptor binding site (43). It has been suggested that antigenic differences within this protein could facilitate repeated HRSV infections (37,59). In addition, positive selection of amino acid changes was observed in the two hypervariable regions of the G protein ectodomain (7,43,71,73,74). One of the hypervariable regions, located in the C-terminal one-third of the G molecule, contains multiple epitopes recognized by monoclonal antibodies (43), suggesting that immune selection of new variants by antibodies may contribute to generation of HRSV diversity.Phylogenetic studies based on sequence analysis of the G protein have identified numerous genotypes in the antigenic groups A and B that show complex circulation patterns, since multiple genotypes of both antigenic groups may circulate within the same season and community, with one or two dominant genotypes being replaced in successive years (13,14,26,27,32,49,50). Each community shows a seasonal circulation

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Section: Discussionmentioning

confidence: 99%

Ten Years of Global Evolution of the Human Respiratory Syncytial Virus BA Genotype with a 60-Nucleotide Duplication in the G Protein Gene

Trento

Casas

Calderón

et al. 2010

J Virol

167

207

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“…Two studies of antibody-mediated response induced by natural infection in humans do, however, show that variable regions of the G protein do induce antibodies specific to strains within group A. In these two studies, human antibodies reacted against expressed or synthetically produced peptides from variable regions of the G protein in a strain-specific fashion (Cane et al, 1996 ;Cane, 1997). We have initiated studies to determine if these ' strain-specific ' G protein antibodies influence which strains cause disease in infants during community RSV outbreaks.…”

Section: Discussionmentioning

confidence: 99%

Circulation patterns of genetically distinct group A and B strains of human respiratory syncytial virus in a community.

Peret

Hall

Schnabel

et al. 1998

Journal of General Virology

402

474

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“…This indicates that, although a high proportion of amino acids can be (52), adaptive evolution may occur at certain sites of the genome. Several linear epitopes have been detected in the G glycoprotein of HRSV-A by analyzing the reaction of human convalescent-phase sera with peptides based on the amino acid sequence of the ectodomain (4,37) and by sequencing escape mutants selected with individual monoclonal antibodies (MAbs). There is a strong association between the positively selected sites identified in this study and the mapped neutralizing epitopes.…”

Section: Discussionmentioning

confidence: 99%

Molecular Evolution and Circulation Patterns of Human Respiratory Syncytial Virus Subgroup A: Positively Selected Sites in the Attachment G Glycoprotein

Zlateva

Lemey

Vandamme

et al. 2004

J Virol

120

129

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Human respiratory syncytial virus (HRSV) is an enveloped virus with a nonsegmented negative-strand RNA genome (family Paramyxoviridae, genus Pneumovirus). HRSV is the major cause of acute lower respiratory tract infections in infants and young children. It is also recognized as an important pathogen in immunocompromised patients and the elderly (12, 58, 65). Two major subgroups of HRSV (HRSV-A and HRSV-B) have been described based on antigenic and sequencing studies (2,6,9,25,34). An unusual feature of HRSV is that repeated infections with both subgroups can occur, despite the development of mucosal and systemic immune responses (18,19,20). Although HRSV-A and -B strains can cocirculate, subgroup A is dominant in more epidemics (1,21,23,33). Several genotypes can cocirculate in a single epidemic season, and different genotypes can predominate in consecutive epidemics (3,7,21,42). In addition, viruses isolated in geographically distant places and in different years may be more closely related than viruses isolated in the same place during the same season (5, 14, 32).The attachment G glycoprotein is a type II integral membrane protein (56, 64) that shows the highest degree of diversity both between and within the two HRSV subgroups (25, 54). The G glycoprotein is one of the main antigens responsible for inducing a neutralizing immune response (11). It is highly glycosylated, and the majority of the potential glycosylation sites are clustered in two mucin-like variable regions of the ectodomain separated by a highly conserved 13-amino-acid motif, which is considered to be the putative site for virus attachment to the cell receptor (8,25,54).Three types of epitopes have been identified in the G molecule: (i) conserved epitopes, shared by subgroups A and B (2, 34), (ii) subgroup-specific epitopes, and (iii) strain-specific or variable epitopes (2, 16). The strain-specific epitopes have been mapped within the hypervariable C-terminal third of the G glycoprotein ectodomain, and there is evidence of progressive accumulation of genetic and antigenic changes in this region (6,14,50).The epidemiology and the possible mechanisms by which HRSV can evade the immune response are still not completely elucidated. The significance of genetic drift and nonprogressive random variation in the molecular evolution of HRSV is a question that remains to be answered. No studies have been conducted on sequence data over more than 10 consecutive HRSV epidemics, and most reports are based on sequencing of only a limited region of the G glycoprotein (41,45,62). In order to investigate the tempo and the mode by which HRSV-A evolves, we sequenced 629 bp of the G glycoprotein ectodomain from 112 subgroup A strains obtained during 19 consecutive years in Belgium (1984Belgium ( to 2002. In the present work, we confirm five previously described amino acid sites and report eight novel sites in the G glycoprotein to be under positive selection. These results suggest that HRSV-A strains are evolving under selective pressure operating in certain codo...

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Analysis of linear epitopes recognised by the primary human antibody response to a variable region of the attachment (G) protein of respiratory syncytial virus

Cited by 75 publications

References 23 publications

Ten Years of Global Evolution of the Human Respiratory Syncytial Virus BA Genotype with a 60-Nucleotide Duplication in the G Protein Gene

Ten Years of Global Evolution of the Human Respiratory Syncytial Virus BA Genotype with a 60-Nucleotide Duplication in the G Protein Gene

Circulation patterns of genetically distinct group A and B strains of human respiratory syncytial virus in a community.

Molecular Evolution and Circulation Patterns of Human Respiratory Syncytial Virus Subgroup A: Positively Selected Sites in the Attachment G Glycoprotein

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