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

Görander, Staffan; Svennerholm, Bo; Liljeqvist, Jan‐Åke

doi:10.1128/jcm.41.8.3681-3686.2003

Cited by 20 publications

(19 citation statements)

References 32 publications

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“…For ELISAs, the sgG recombinant protein was weakly reactive with sera from naturally infected macaques, suggesting that sgG is simply not capable of inducing a strong B-cell response, nor is its authentic counterpart from B virus. Similar observations have been made for HSV-2-infected humans with sgG-2, which induces only a weak antibody response late in infection relative to membrane-associated gG (17).…”

Section: Discussionsupporting

confidence: 64%

“…The secreted N-terminal fragment of gG appeared to have little diagnostic value, as low serum reactivity was observed with the sgG antigen even when readily detectable mgG-specific antibodies were present. A recently developed sgG-2-based ELISA for HSV-2 antibody detection similarly demonstrated a reduced sensitivity relative to ELISA with mgG-2 or whole gG-2 (17,34). We demonstrated in this study that the diagnostic sensitivity of the mgG-based ELISA is lower than that of the gB-, gC-, or gD-based ELISA.…”

Section: Discussionmentioning

confidence: 68%

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Production of Herpes B Virus Recombinant Glycoproteins and Evaluation of Their Diagnostic Potential

et al. 2005

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B virus (cercopithecine herpesvirus 1) is the only deadly alphaherpesvirus that is zoonotically transmissible from macaques to humans. The detection of humoral immune responses is the method of choice for the rapid identification of B virus-infected animals. We evaluated the diagnostic potential of recombinant B virus glycoproteins for the detection of immunoglobulin G (IgG) antibodies in monkey and human sera. Glycoproteins B, C, and E and secreted (sgG) and membrane-associated (mgG) segments of glycoprotein G (gG) were expressed in the baculovirus expression system, while gD was expressed in CHO cells. We developed recombinant protein-based IgG enzyme-linked immunosorbent assays (ELISAs) and compared their diagnostic efficacies by using B virus antibody-negative (n ‫؍‬ 40) and -positive (n ‫؍‬ 75) macaque sera identified by a whole antigenbased ELISA and Western blotting. The diagnostic sensitivities of the gB-, gC-, gD-, and mgG-ELISAs were 100, 97.3, 88.0, and 80.0%, respectively. The specificities of the gB-, gC-, and gD-ELISAs and of the mgG-ELISA were 100 and 97.5%, respectively. In contrast, the sensitivities and specificities of sgG-and gE-ELISAs were low, suggesting that sgG and gE are less effective diagnostic antigens. Sera from nonmacaque monkeys crossreacted with gB, gC, and gD, and only baboon sera reacted weakly with mgG. Human herpes simplex virus type 1 (HSV-1)-and HSV-2-positive sera pools reacted with gB and gD, whereas sera from B virus-infected individuals reacted with all four antigens. These data indicate that gB, gC, gD, and mgG have a high diagnostic potential for B virus serodiagnosis in macaques, whereas mgG may be a valuable antigen for discrimination between antibodies induced by B virus and those induced by other, closely related alphaherpesviruses, including HSV-1 and -2.Human infection with B virus (also called cercopithecine herpesvirus 1, monkey B virus, and herpes B virus) is the most feared occupational hazard among individuals working with macaque monkeys, since fatality is often the outcome of infection, which proceeds in the absence of effective antiviral therapy (25,56). The use of macaques in research has been steadily growing over the last decade and is expected to rise quickly in the near future due to the increasing demands for these animals for use in HIV/AIDS investigations, vaccine trials, drug testing, and research into bioterrorism agents. As macaque usage increases, frequencies of human exposures to B virus are increasing as well. Rapid and accurate diagnostic tests are urgently needed to aid in the early identification of clinical cases, which is essential for a timely initiation of antiviral therapies in zoonotically infected humans. In addition to human diagnostics, enhanced assays are required for monitoring specific-pathogen-free (SPF) macaque colonies established by the National Institutes of Health for the breeding of B virusfree animals (55), as these animals often demonstrate only very low levels of antibody.Unfortunately, a direct diagnosis of infectio...

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 68%

Production of Herpes B Virus Recombinant Glycoproteins and Evaluation of Their Diagnostic Potential

et al. 2005

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“…This immune escape might be of importance for the pathogenesis of HSV-2, in particular for the establishment of HSV-2 infection in individuals that are already infected with HSV-1. The acquired immune responses to HSV-1 and HSV-2 are, with the exception of the immune response to the gG-2 protein, highly cross-reactive (43)(44)(45)(46)). Yet, HSV-2 manages to infect HSV-1-seropositive individuals as efficiently as it infects individuals with no prior HSV exposure (47), perhaps as a consequence of a gG-2-induced ROS-mediated suppression of specific lymphocyte subsets.…”

Section: Discussionmentioning

confidence: 99%

A Proinflammatory Peptide from Herpes Simplex Virus Type 2 Glycoprotein G Affects Neutrophil, Monocyte, and NK Cell Functions

Bellner

Thorén²,

Nygren

et al. 2005

The Journal of Immunology

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We have identified a synthetic peptide derived from the secreted portion of HSV type 2 glycoprotein G, denoted gG-2p20, which has proinflammatory properties in vitro. The gG-2p20 peptide, corresponding to aa 190–205 of glycoprotein G-2, was a chemoattractant for both monocytes and neutrophils in a dose-dependent fashion, and also induced the release of reactive oxygen from these cells. The receptor mediating the responses was identified as the formyl peptide receptor. The gG-2p20-induced activation of phagocytes had a profound impact on NK cell functions. The reactive oxygen species produced by gG-2p20-activated phagocytes both inhibited NK cell cytotoxicity and accelerated the apoptotic cell death in NK cell-enriched lymphocyte populations. Hence, we have for the first time been able to identify a potential function of the secreted portion of HSV-2 glycoprotein G. We propose that the proinflammatory gG-2p20 peptide identified could contribute to a reduced function and viability of NK cells during HSV-2 infection due to its ability to recruit and activate phagocytic cells.

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“…The type common antibody response against HSV is mostly attributed to gB, a 904-aa protein and a major component of infected cell membranes and virion envelopes (Vestergaard, 1980;Cai et al, 1988). Although the aa similarity between HSV-1 and HSV-2 is high, the envelope gG, a 238-aa long chemokine-binding protein, is the only HSV antigen known to induce type-specific antibody responses and is therefore used in serological assays to discriminate between HSV-1 and HSV-2 infections (Ashley, 1998;Görander et al, 2003). These glycoprotein sequences were selected to obtain peptides with antigenic epitopes on the basis of prediction analysis by Kolaskar and Tongaonkar method.…”

Section: Discussionmentioning

confidence: 99%

Identification of an immunodominant epitope in glycoproteins B and G of herpes simplex viruses (HSVs) using synthetic peptides as antigens in assay of antibodies to HSV in herpes simplex encephalitis patients

Ss¹,

Nh²,

Nn³

et al. 2014

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Summary. -Herpes simplex encephalitis (HSE) is a severe viral infection of the central nervous system (CNS). Assay of antibody response is widely used in diagnostics of HSE. The aim of this study was to identify an immunodominant epitope determining the antibody response to herpes simplex viruses (HSVs) in cerebrospinal fluid (CSF) of HSE patients. The synthetic peptides that resembled type-common as well as type-specific domains of glycoproteins B (gB) and G (gG) of these viruses were evaluated for binding with IgM and IgG antibodies in CSF samples from HSE and non-HSE patients in ELISA. The QLHDLRF peptide, derived from gB of HSV was found to be an immunodominant epitope in the IgM and IgG antibody response. The patients with confirmed and suspected HSE showed in ELISA against this peptide 26% and 23% positivities for IgM, 43% and 37% positivities for IgG and 17% and 15% for both IgM and IgG antibodies, respectively. The total positivities of 86% and 75% for both IgM and IgG antibodies were obtained in the patients with confirmed and suspected HSE, respectively. These results demonstrate that a synthetic peptide-based diagnostics of HSE can be an efficient and easily accessible alternative. This is the first report describing the use of synthetic peptides derived from HSVs in diagnostics of HSE using patientsʹ CSF samples.

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

Cited by 20 publications

References 32 publications

Production of Herpes B Virus Recombinant Glycoproteins and Evaluation of Their Diagnostic Potential

Production of Herpes B Virus Recombinant Glycoproteins and Evaluation of Their Diagnostic Potential

A Proinflammatory Peptide from Herpes Simplex Virus Type 2 Glycoprotein G Affects Neutrophil, Monocyte, and NK Cell Functions

Identification of an immunodominant epitope in glycoproteins B and G of herpes simplex viruses (HSVs) using synthetic peptides as antigens in assay of antibodies to HSV in herpes simplex encephalitis patients

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