Monoclonal antibodies and human sera directed to the secreted glycoprotein G of herpes simplex virus type 2 recognize type-specific antigenic determinants

Liljeqvist, Jan‐Åke; Trybala, Edward; Hoebeke, Johan; Svennerholm, Bo; Bergström, Tomas

doi:10.1099/0022-1317-83-1-157

Cited by 24 publications

(27 citation statements)

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“…WB can therefore be used as a sensitive and specific method for confirmation of the presence of type-specific anti-gG-2 antibodies. In contrast, antisgG-2 antibodies identify mostly nonlinear epitopes, which by WB have no reactivity to virus-infected cell lysates or purified sgG-2 antigen prepared under reducing conditions (18). This finding makes WB unsuitable as an alternative and sensitive method for the detection of anti-sgG-2 antibodies.…”

Section: Vol 41 2003 Glycoprotein G Of Hsv-2 and Type-specific Seromentioning

confidence: 65%

“…Immunosorbent affinity chromatography-purified sgG-2 (0.75 mg/ml) was prepared as described earlier (18) and coated at a 1:3,000 dilution in carbonate buffer (pH 9.6) on Maxisorp microtiter plates (Nalge Nunc International). Peroxidase-conjugated goat anti-human IgG (Jackson ImmunoResearch Laboratories) was used as the conjugate at a 1:3,000 dilution, with o-phenylenediamine used as the substrate.…”

Section: Cells and Virusesmentioning

confidence: 99%

“…In addition, a type-specific immunoglobulin G (IgG) antibody response was detected in sera from HSVinfected patients by using sgG-2 as the antigen (18). In the present study, the performance of immunosorbent purified sgG-2 in an enzyme-linked immunosorbent assay (ELISA) format (sgG-2 ELISA) was evaluated with large panels of sera collected from patients with isolation-proven HSV-1 or HSV-2 infections.…”

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confidence: 99%

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Secreted Portion of Glycoprotein G of Herpes Simplex Virus Type 2 Is a Novel Antigen for Type-Discriminating Serology

2003

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The secreted portion of glycoprotein G (sgG-2) of herpes simplex virus type 2 (HSV-2) was evaluated as a novel antigen in an enzyme-linked immunosorbent assay (ELISA) format for detection of type-specific immunoglobulin G (IgG) antibodies in HSV-2-infected patients. The results were compared with those obtained by a commercially available assay, the HerpeSelect 2 ELISA (the FOCUS2 assay). Five different panels of sera were analyzed: panel A consisted of 109 serum samples from patients with a culture-proven HSV-1 infection that were Western blotting (WB) negative for HSV-2; panel B consisted of 106 serum samples from patients with a culture-proven recurrent HSV-2 infection that were WB positive for HSV-2; panel C consisted of 100 serum samples with no detectable IgG antibodies against HSV-1 and HSV-2; panel D consisted of 70 HSV-2 negative "tricky" serum samples containing antinuclear IgG antibodies or IgM antibodies against other viruses or bacteria; and panel E consisted of consecutive serum samples from 21 patients presenting with a first episode of HSV-2-induced lesions. When sera in panels A to C were analyzed, the sgG-2 ELISA and the FOCUS2 assay both showed sensitivities and specificities of >98%. In total, among the samples in panel D, 13 serum samples (19%) were false positive by the FOCUS2 assay and 1 serum sample (1.4%) was false positive by the sgG-2 ELISA. When the sera in panel E were analyzed, the sgG-2 ELISA detected seroconversion somewhat later than WB or the FOCUS2 assay did. We conclude that sgG-2 induces an HSV-2 type-specific antibody response and can be used for type-discriminating serology.

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Section: Vol 41 2003 Glycoprotein G Of Hsv-2 and Type-specific Seromentioning

confidence: 65%

Section: Cells and Virusesmentioning

confidence: 99%

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Secreted Portion of Glycoprotein G of Herpes Simplex Virus Type 2 Is a Novel Antigen for Type-Discriminating Serology

2003

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“…Because our preparation of mgG was derived from HSV-2 virions and the virus-infected cells, one cannot exclude the possibility that part of its binding activity was due to the presence of a noncleaved precursor protein composed of both mgG and sgG. Although sgG was not detected in preparations of mgG purified from infected cells based on its affinity to Helix pomatia lectin, this form of gG has an overall net positive charge and its heparin binding activity has been demonstrated (21). More importantly, we also observed that purified mgG bound to cultured cells, and the reduction of this activity by PI-88 suggested that mgG could interact with negatively charged molecules at the cell surface.…”

Section: Discussionmentioning

confidence: 91%

“…The gG gene of HSV-2 codes for a 699-amino-acid-long precursor protein which is processed by proteolytic cleavage to generate a secreted amino-terminal fragment of gG (sgG) and a carboxy-terminal cell-and viral membrane-associated mature gG (mgG) (2,23,32,33). The sgG is secreted into the extracellular medium (32) and can be purified from culture medium based on its affinity for heparin (21). The mgG is heavily O glycosylated, and the amino-terminal region occupied with clustered O-linked glycans constitutes more than half of the mgG amino acid sequence.…”

Section: Discussionmentioning

confidence: 99%

Herpes Simplex Virus Type 2 Glycoprotein G Is Targeted by the Sulfated Oligo- and Polysaccharide Inhibitors of Virus Attachment to Cells

Adamiak

Ekblad

Bergström

et al. 2007

J Virol

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Variants of herpes simplex virus type 2 (HSV-2) generated by virus passage in GMK-AH1 cells in the presence of the sulfated oligosaccharide PI-88 were analyzed. Many of these variants were substantially resistant to PI-88 in their initial infection of cells and/or their cell-to-cell spread. The major alteration detected in all variants resistant to PI-88 in the initial infection of cells was a frameshift mutation(s) in the glycoprotein G (gG) gene that resulted in the lack of protein expression. Molecular transfer of the altered gG gene into the wild-type background confirmed that the gG-deficient recombinants were resistant to PI-88. In addition to PI-88, all gG-deficient variants of HSV-2 were resistant to the sulfated polysaccharide heparin. The gGdeficient virions were capable of attaching to cells, and this activity was relatively resistant to PI-88. In addition to having a drug-resistant phenotype, the gG-deficient variants were inefficiently released from infected cells. Purified gG bound to heparin and showed the cell-binding activity which was inhibited by PI-88. Many PI-88 variants produced syncytia in cultured cells and contained alterations in gB, including the syncytium-inducing L792P amino acid substitution. Although this phenotype can enhance the lateral spread of HSV in cells, it conferred no virus resistance to PI-88. Some PI-88 variants also contained occasional alterations in gC, gD, gE, gK, and UL24. In conclusion, we found that glycoprotein gG, a mucin-like component of the HSV-2 envelope, was targeted by sulfated oligo-and polysaccharides. This is a novel finding that suggests the involvement of HSV-2 gG in interactions with sulfated polysaccharides, including cell surface glycosaminoglycans.It is well-established that cell surface heparan sulfate (HS) chains provide the binding sites for the initial interactions with cells of many viruses, including herpes simplex virus type 1 (HSV-1) and HSV-2 (38). The two types of HSV differ in their interactions with HS with respect to both the viral glycoproteins and the HS motifs involved. In particular, glycoprotein C (gC) of HSV-1 was identified as a component of the viral envelope that interacts with HS/heparin chains, thus mediating the attachment of the virus to cells (15). Although gC of HSV-2 can bind to HS/heparin chains and was found to be responsible for several HSV type-specific differences, such as polycation (28) and the hypertonic medium (36) resistance of HSV-2 infection of cells, this protein did not mediate HSV-2 attachment to cells (11). Instead, gB, another HS-binding component of the HSV envelope, was identified as the major virus attachment protein (5). In addition to gB and gC, gD of HSV-1, but not its HSV-2 homolog, can bind to HS chains modified by several isoforms of 3-O-sulfotransferase (31), an interaction that triggers HSV-1 entry into cells. Thus, interaction of HSV with HS seems to be a complex process that involves several kinds of viral proteins promoting virus attachment to and entry into cells.Compounds such as sulfa...

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Viral O‐GalNAc peptide epitopes: a novel potential target in viral envelope glycoproteins

Olofsson

Blixt

Bergström

et al. 2015

Reviews in Medical Virology

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Viral envelope glycoproteins are major targets for antibodies that bind to and inactivate viral particles. The capacity of a viral vaccine to induce virus-neutralizing antibodies is often used as a marker for vaccine efficacy. Yet the number of known neutralization target epitopes is restricted owing to various viral escape mechanisms. We expand the range of possible viral glycoprotein targets, by presenting a previously unknown type of viral glycoprotein epitope based on a short peptide stretch modified with small O-linked glycans. Besides being immunologically active, these epitopes have a high potential for antigenic variation. Thus, sera from patients infected with EBV develop individual IgG responses addressing the different possible glycopeptide glycoforms of one short peptide backbone that reflect individual variations in the course of virus infection. In contrast, in HSV type 2 meningitis patients, CSF antibodies are focussed to only one single glycoform peptide of a major viral glycoprotein. Thus, dependent on the viral disease, the serological response may be variable or constant with respect to the number of targeted peptide glycoforms. Mapping of these epitopes relies on a novel three-step procedure that identifies any reactive viral O-glycosyl peptide epitope with respect to (i) relevant peptide sequence, (ii) the reactive glycoform out of several possible glycopeptide isomers of that peptide sequence, and (iii) possibly tolerated carbohydrate or peptide structural variations at glycosylation sites. In conclusion, the viral O-glycosyl peptide epitopes may be of relevance for development of subunit vaccines and for improved serodiagnosis of viral diseases. Copyright © 2015 John Wiley & Sons, Ltd.

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Monoclonal antibodies and human sera directed to the secreted glycoprotein G of herpes simplex virus type 2 recognize type-specific antigenic determinants

Cited by 24 publications

References 50 publications

Secreted Portion of Glycoprotein G of Herpes Simplex Virus Type 2 Is a Novel Antigen for Type-Discriminating Serology

Secreted Portion of Glycoprotein G of Herpes Simplex Virus Type 2 Is a Novel Antigen for Type-Discriminating Serology

Herpes Simplex Virus Type 2 Glycoprotein G Is Targeted by the Sulfated Oligo- and Polysaccharide Inhibitors of Virus Attachment to Cells

Viral O‐GalNAc peptide epitopes: a novel potential target in viral envelope glycoproteins

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