The dominant linear neutralizing antibody-binding site of glycoprotein gp86 of human cytomegalovirus is strain specific

Urban, Margit; Britt, William J.; Mach, Michael

doi:10.1128/jvi.66.3.1303-1311.1992

Cited by 107 publications

(65 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This region was reported to be a dominant linear antibody-binding site in HCMV (31) and MCMV (34). Furthermore, human sera capable of neutralizing HCMV had epitopes within the amino-terminal region (31). The corresponding part of gH of HHV-7 was immunogenic in mice as was presented in this paper.…”

Section: Discussionsupporting

confidence: 53%

“…The hydrophobic regions at the N-terminus and C-terminus of HHV-7 gH ORF probably interfered with the expression of the fusion protein. Since possible immunogenic regions of HHV-7 gH existed in a manner similar to other (3-herpesviruses, we subcloned part of the gH gene (pH45), which was mapped to the N-terminal, into the expression vector that has been successfully employed for HCMV (31) and murine cytomegalovirus (34). Thus, a polypeptide with an apparent MW of 40 kDa including the GST portion (pH45 fusion protein) was expressed.…”

Section: Expression Of the Hhv-7 Gh And Gl Genes In E Colimentioning

confidence: 99%

See 1 more Smart Citation

Characterization of Glycoprotein H and L of Human Herpesvirus 7

Mukai

Hata²,

Isegawa³

et al. 1997

Microbiology and Immunology

View full text Add to dashboard Cite

The genes encoding the glycoproteins H (gH) and L (gL) of human herpesvirus 7 (HHV-7) have been identified. The gH open reading frame (ORF) was 2,070 base pairs in length and encoded a predicted 690 amino-acid protein. The gH contained characteristics of a transmembrane glycoprotein including 10 consensus N-linked glycosylation sites, 12 cysteine residues, a potential amino-terminal signal sequence and a predicted transmembrane segment located near the carboxyl terminus. The gL ORF was 738 base pairs in length and encoded a predicted 246 amino-acid protein. Four possible N-glycosylation sites and 6 cysteine residues existed within gL. The predicted amino-acid sequences of the HHV-7 gH and human herpesvirus 6 variant A (HHV-6A) gH gene products exhibited 23.6% identity to each other, and those of the gL gene products had 26.0% identity. Upon in vitro translation of the gL gene, the addition of microsomal membranes resulted in two modified products with molecular weights of 32 kDa and 35 kDa from the unmodified initial translation product of 26 kDa. An amino-terminal portion of gH and the full length of gL were expressed as glutathione S-transferase fusion proteins, and these proteins were used to raise immune sera in mice. Lysates of cells infected with HHV-7 were subjected to immunoprecipitation analysis. Approximate molecular weights of 33, 37, 80 and 90 kDa polypeptides were immunoprecipitated with antibodies against the gH protein. Antibodies against the gL protein polypeptides with the same molecular weights were also precipitated, and were observed with the antibodies against the gH protein. These results suggest that HHV-7 gH and gL may form a heterodimeric complex with each other in HHV-7 infected cells, as has been reported for other herpesviruses.

show abstract

Section: Discussionsupporting

confidence: 53%

Section: Expression Of the Hhv-7 Gh And Gl Genes In E Colimentioning

confidence: 99%

Characterization of Glycoprotein H and L of Human Herpesvirus 7

Mukai

Hata²,

Isegawa³

et al. 1997

Microbiology and Immunology

View full text Add to dashboard Cite

show abstract

“…Images were processed using MetaView software and Adobe Photoshop. Antibodies: gB-specific human mab C23 (TI-23) [41], gN-specific murine mab 14-16A [71], gH-specific murine mab SA4 [72], murine anti-HA (Sigma Aldrich, Germany) and murine anti-GST (BIOZOL, Germany).…”

Section: Transient Protein Expression and Image Analysismentioning

confidence: 99%

B Cell Repertoire Analysis Identifies New Antigenic Domains on Glycoprotein B of Human Cytomegalovirus which Are Target of Neutralizing Antibodies

et al. 2011

View full text Add to dashboard Cite

Human cytomegalovirus (HCMV), a herpesvirus, is a ubiquitously distributed pathogen that causes severe disease in immunosuppressed patients and infected newborns. Efforts are underway to prepare effective subunit vaccines and therapies including antiviral antibodies. However, current vaccine efforts are hampered by the lack of information on protective immune responses against HCMV. Characterizing the B-cell response in healthy infected individuals could aid in the design of optimal vaccines and therapeutic antibodies. To address this problem, we determined, for the first time, the B-cell repertoire against glycoprotein B (gB) of HCMV in different healthy HCMV seropositive individuals in an unbiased fashion. HCMV gB represents a dominant viral antigenic determinant for induction of neutralizing antibodies during infection and is also a component in several experimental HCMV vaccines currently being tested in humans. Our findings have revealed that the vast majority (>90%) of gB-specific antibodies secreted from B-cell clones do not have virus neutralizing activity. Most neutralizing antibodies were found to bind to epitopes not located within the previously characterized antigenic domains (AD) of gB. To map the target structures of these neutralizing antibodies, we generated a 3D model of HCMV gB and used it to identify surface exposed protein domains. Two protein domains were found to be targeted by the majority of neutralizing antibodies. Domain I, located between amino acids (aa) 133–343 of gB and domain II, a discontinuous domain, built from residues 121–132 and 344–438. Analysis of a larger panel of human sera from HCMV seropositive individuals revealed positivity rates of >50% against domain I and >90% against domain II, respectively. In accordance with previous nomenclature the domains were designated AD-4 (Dom II) and AD-5 (Dom I), respectively. Collectively, these data will contribute to optimal vaccine design and development of antibodies effective in passive immunization.

show abstract

“…Similarly, a strain-specific N-terminal epitope (34-43 aa), capable of inducing neutralising antibodies has been shown for glycoprotein H [111]. However, the significance of strain-specific and strain-common epitopes is not completely understood.…”

Section: Interaction With the Host Immune Systemmentioning

confidence: 99%

Genetic polymorphisms among human cytomegalovirus (HCMV) wild‐type strains

Pignatelli

Monte

Rossini

et al. 2004

Reviews in Medical Virology

134

126

View full text Add to dashboard Cite

Human cytomegalovirus (HCMV) clinical isolates display genetic polymorphisms in multiple genes. Some authors have suggested that those polymorphisms may be implicated in HCMV-induced immunopathogenesis, as well as in strain-specific behaviours, such as tissue-tropism and ability to establish persistent or latent infections. This review summarises the features of the main clustered HCMV polymorphic open reading frames and also briefly cites other variable loci within the viral genome. The implications of gene polymorphisms are discussed in terms of potentially advantageous higher fitness obtained by the strain, but also taking into account that the published data are often speculative. The last section of this review summarises and critically analyses the main literature reports about the linkage of strain specific genotypes with clinical manifestations of HCMV disease in different patient populations affected by severe cytomegalovirus infections, namely immunocompromised subjects and congenitally infected newborns.

show abstract

The dominant linear neutralizing antibody-binding site of glycoprotein gp86 of human cytomegalovirus is strain specific

Cited by 107 publications

References 44 publications

Characterization of Glycoprotein H and L of Human Herpesvirus 7

Characterization of Glycoprotein H and L of Human Herpesvirus 7

B Cell Repertoire Analysis Identifies New Antigenic Domains on Glycoprotein B of Human Cytomegalovirus which Are Target of Neutralizing Antibodies

Genetic polymorphisms among human cytomegalovirus (HCMV) wild‐type strains

Contact Info

Product

Resources

About