Characterization of virus-specific and cross-reactive monoclonal antibodies to Herpesvirus simiae (B virus)

Blewett, Earl L.; Black, Darla H.; Eberle, R.

doi:10.1099/0022-1317-77-11-2787

Cited by 18 publications

(12 citation statements)

References 32 publications

(9 reference statements)

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“…The 48-and 20-kDa bands were weak and could be seen only after long exposures of immunoblots to X-ray films. The polypeptides recognized by the produced monospecific antisera were in size agreement with the previously reported molecular masses of selected B virus glycoproteins (7,41,48). These data validate that the antigenic and immunogenic properties of the prepared recombinant proteins are similar to those of viral glycoproteins produced during B virus infection.…”

Section: Resultssupporting

confidence: 76%

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: Resultssupporting

confidence: 76%

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

et al. 2005

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“…Baboon CMV was detected using 2 monoclonal antibodies, 35C7 (1:1000) and 37E12.1D1 (1:10), generated against bCMV-infected cell proteins by Dr E. Blewett, as described. 26 Baboon LCV was detected using a monoclonal antibody directed against the BZLF1 protein of EBV (1:50, M7005, clone BZ; DAKO Cytomation, Carpinteria, CA). 1 To ensure that the tissue could be immunostained, sections were also stained for vimentin (1:100, M7020, clone Vim 3B4; DAKO Cytomation).…”

Section: Detection Of Bcmv and Blcv In Thymi By Immunohistochemistrymentioning

confidence: 99%

De novo generation of CD4 T cells against viruses present in the host during immune reconstitution

Kalina

Zhao

et al. 2005

Blood

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T cells recognizing self-peptides are typically deleted in the thymus by negative selection. It is not known whether T cells against persistent viruses (eg, herpesviruses) are generated by the thymus (de novo) after the onset of the infection. Peptides from such viruses might be considered by the thymus as self-peptides, and T cells specific for these peptides might be deleted (negatively selected). Here we demonstrate in baboons infected IntroductionPatients who have undergone hematopoietic cell transplantation, AIDS patients, patients with congenital thymic hypoplasia, and elderly persons lack naive T cells because of insufficient generation of T cells de novo (thymopoiesis). [1][2][3][4][5][6] Ways to improve de novo generation have recently been studied using prothymopoietic cytokines such as interleukin-7 (IL-7) or keratinocyte growth factor, 7-9 thymic transplantation, 5 or a thymic organoid ("artificial thymus"). 10 It is not known whether improved thymopoiesis might result in more T cells only for pathogens typically absent from the body (eg, neopathogens such as Ebola virus or cleared recall pathogens such as measles virus) or for pathogens or malignant cells present in the body (eg, herpesviruses that infected the host before transplantation or the leukemia that necessitated hematopoietic cell transplantation). The latter T cells may be more important, as suggested by our recent study of 115 recipients of hematopoietic cell transplants (Storek et al 11 and J.S., unpublished observations, 2001). Of 158 infections with a known etiologic agent that occurred after engraftment (primarily caused by T-cell deficiency), 67 of 158 (42%) infections were clearly caused by endogenous microorganisms (herpesviruses), and 34 of 158 (22%) infections were likely caused by endogenous microorganisms (digestive tract bacteria and yeasts). Relapse of the underlying hematologic malignancy occurred after transplantation in at least 15% of patients.Human cytomegalovirus (CMV) and Epstein-Barr virus (EBV) are examples of viruses present in seropositive hosts during posttransplantation immune reconstitution. They cause serious disease in recipients of transplant (CMV pneumonia or gastroenteritis, EBV lymphoma). 12,13 Seropositivity is a marker of infection because after primary infection of humans with human CMV or EBV, anti-CMV/EBV antibodies are generated for life. In addition, the virus is always present in the infected human host-CMV in myeloid cells and EBV in B cells and pharyngeal epithelial cells. 14 Baboon CMV (bCMV, SA6-like virus) and baboon lymphocryptovirus (bLCV, cercopithecine herpesvirus 12, herpesvirus papio) infections of baboons closely resemble CMV and EBV infections of humans. [15][16][17] As do humans, baboons typically become infected with bCMV and bLCV during childhood. [18][19][20] To address whether CD4 T cells against persistent viruses can be generated de novo, we searched for YFP-marked CD4 T cells specific for bCMV or bLCV in bCMV/bLCV-seropositive baboons that underwent transplantation with auto...

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“…The mAbs 12F5.C1, 2G12.D12.D4, 6E10.D7 appeared to recognize linear epitopes, while the other mAbs likely recognized conformational epitopes. In comparison with others, we obtained a greater proportion of mAbs reactive with conformational epitopes possibly because we used immunogens in which protein conformation was partially or fully preserved [ 21 ]. B virus VP13/14 was identified as the target protein for the B virus specific mAb 12F5.C1.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, however, when tested by the mAb-CE test, these mAbs were competed by HSV-1/HSV-2 antibodies. Blocking binding of the Category-II mAbs to their B virus-specific epitopes may be caused by steric hindrance due to binding of the HSV-common antibodies to a nearby cross-reacting epitopes [ 5 , 21 ]. However, epitope mapping of the Category-II mAbs may provide the identification and synthesis of B virus-specific epitopes that can be used in peptide-based assays for differential serological diagnosis of B virus infection in humans with pre-existing HSV-1/HSV-2 antibodies.…”

Section: Discussionmentioning

confidence: 99%

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Identification of unique B virus (Macacine Herpesvirus 1) epitopes of zoonotic and macaque isolates using monoclonal antibodies

Katz¹,

Wei²,

Gowda³

et al. 2017

PLoS ONE

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Our overall aim is to develop epitope-based assays for accurate differential diagnosis of B virus zoonotic infections in humans. Antibodies to cross-reacting epitopes on human-simplexviruses continue to confound the interpretation of current assays where abundant antibodies exist from previous infections with HSV types 1 and 2. To find B virus-specific epitopes we cloned ten monoclonal antibodies (mAbs) from the hybridomas we produced. Our unique collection of rare human sera from symptomatic and asymptomatic patients infected with B virus was key to the evaluation and identification of the mAbs as reagents in competition ELISAs (mAb-CE). The analysis of the ten mAbs revealed that the target proteins for six mAbs was glycoprotein B of which two are reactive to simian simplexviruses and not to human simplexviruses. Two mAbs reacted specifically with B virus glycoprotein D, and two other mAbs were specific to VP13/14 and gE-gI complex respectively. The mAbs specific to VP13/14 and gE-gI are strain specific reacting with B virus isolates from rhesus and Japanese macaques and not with isolates from cynomolgus and pigtail macaques. The mAb-CE revealed that a high proportion of naturally B virus infected rhesus macaques and two symptomatic humans possess antibodies to epitopes of VP13/14 protein and on the gE-gI complex. The majority of sera from B virus infected macaques and simplexvirus-infected humans competed with the less specific mAbs. These experiments produced a novel panel of mAbs that enabled B virus strain identification and confirmation of B virus infected macaques by the mAb-CE. For human sera the mAb-CE could be used only for selected cases due to the selective B virus strain-specificity of the mAbs against VP13/14 and gE/gI.To fully accomplish our aim to provide reagents for unequivocal differential diagnosis of zoonotic B virus infections, additional mAbs with a broader range of specificities is critical.

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Characterization of virus-specific and cross-reactive monoclonal antibodies to Herpesvirus simiae (B virus)

Cited by 18 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

De novo generation of CD4 T cells against viruses present in the host during immune reconstitution

Identification of unique B virus (Macacine Herpesvirus 1) epitopes of zoonotic and macaque isolates using monoclonal antibodies

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