A pre-eclampsia-associated Epstein-Barr virus antibody cross-reacts with placental GPR50

Elliott, Serra E.; Parchim, Nicholas; Kellems, Rodney E.; Xia, Yang; Soffici, Alex R.; Daugherty, Patrick S.

doi:10.1016/j.clim.2016.05.002

Cited by 8 publications

(12 citation statements)

References 56 publications

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“…The prevalence of each epitope is noted, which is defined as the proportion of specimens that bound the epitope. Some of these epitopes have been reported previously [6,33–35]. Thus, a modest number of prominent linear viral epitopes were bound by >30% of the specimens analyzed.…”

Section: Resultssupporting

confidence: 58%

“…Bacterial proteins chosen for validation were Streptolysin O, corresponding to the second most prevalent Streptococcus epitope (Table 2), and Extracellular matrix protein-binding protein emp, corresponding to most prevalent Staphylococcus epitope (Table 2). In all cases, K-TOPE found prominent peaks in the histograms that corresponded to reported epitopes (Fig 4) [6,33,35,40]. Additionally, K-TOPE identified an immunogenic region of GA-repeats from positions 100-350 in the analysis of EBNA1 [23].…”

Section: Resultsmentioning

confidence: 99%

“…For EBNA1, RRPFF was chosen because it was noted that RRPFF antibodies were found in the serum of healthy individuals [33]. KRPSCIGCK was noted as an EBNA1 epitope that was preferentially targeted by pre-eclamptic women, but was also targeted by healthy controls [6]. The motif XPEFXGSXX was discovered and inferred to correspond to VPEFKGSLP in Staphylococcus aureus using protein database searches [40].…”

Section: Methodsmentioning

confidence: 99%

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A general approach for identifying protein epitopes targeted by antibody repertoires using whole proteomes

Paull

Johnston

Ibsen

et al. 2019

Preprint

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28Antibodies are essential to functional immunity, yet the epitopes targeted by antibody 29 repertoires remain largely uncharacterized. To aid in characterization, we developed a 30 generalizable strategy to identify antibody-binding epitopes within individual proteins and entire 31 proteomes. Specifically, we selected antibody-binding peptides for 273 distinct sera out of a 32 random library and identified the peptides using next-generation sequencing. To identify 33 antibody-binding epitopes and the antigens from which these epitopes were derived, we tiled the 34 sequences of candidate antigens into short overlapping subsequences of length k (k-mers). We 35 used the enrichment over background of these k-mers in the antibody-binding peptide dataset to 36 identify antibody-binding epitopes. As a positive control, we used this approach, termed K-mer 37 Tiling of Protein Epitopes (K-TOPE), to identify epitopes targeted by monoclonal and polyclonal 38 antibodies of well-characterized specificity, accurately recovering their known epitopes. K-39 TOPE characterized a commonly targeted antigen from Rhinovirus A, identifying three epitopes 40 recognized by antibodies present in 83% of sera (n = 250). An analysis of 2,908 proteins from 41 400 viral taxa that infect humans revealed seven enterovirus epitopes and five Epstein-Barr virus 42 epitopes recognized by >30% of specimens. Analysis of Staphylococcus and Streptococcus 43 proteomes similarly revealed six epitopes recognized by >40% of specimens. These common 44 viral and bacterial epitopes exhibited excellent agreement with previously mapped epitopes.45 Additionally, we identified 30 HSV2-specific epitopes that were 100% specific against HSV1 in 46 novel and previously reported antigens. The K-TOPE approach thus provides a powerful new 47 tool to elucidate the organisms, antigens, and epitopes targeted by human antibody repertoires. 48 49 50 Introduction 51 52 Immunological memory allows for rapid antibody responses towards diverse antigens 53 long after initial exposure. For example, the adaptive immune response to many vaccinations is 54 often sustained throughout an individual's lifetime [1]. This immunological information is 55 archived within the genes encoding B-cell and T-cell receptors along with the corresponding 56 receptor structures, but has proven difficult to characterize in a comprehensive manner. The 57 ability to more fully interrogate immunological memory could reveal exposures to pathogens, 58 commensal organisms, and allergens. Such information has proven useful for correlating 59 antibody responses with disease outcomes to design more effective vaccines [2]. A detailed 60 record of immune exposures can also facilitate the identification of biomarkers to diagnose 61 infectious [3], autoimmune [4], and allergic conditions [5]. Furthermore, the capability to 62 broadly characterize antibody repertoires at the epitope level could be used to identify conserved 63 pathogen epitopes [6] and tumor specific antigen epitopes [7] to aid in therapeutic disco...

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Section: Resultssupporting

confidence: 58%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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A general approach for identifying protein epitopes targeted by antibody repertoires using whole proteomes

Paull

Johnston

Ibsen

et al. 2019

Preprint

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“…Интеграционный анализ транскриптомных данных по микроРНК показал, что недостаточность витамина D стимулирует рост вируса Эпштейна -Барра (который, в свою очередь, способствует развитию рассеянного склероза через нарушение регуляции экспрессии микроРНК mir-15a, mir-48d, mir-30d, mir-145, mir-363, has-let-7e, mir-30a, let-7b и mir-146a) [40]. Отметим, что инфицирование беременных вирусом Эпштейна -Барра стимулирует формирование антифосфолипидных антител [41], патологии плаценты [42], преэклампсии и несовместимых с жизнью неврологических отклонений у плода [43].…”

Section: действие витамина D против других вирусовunclassified

About antiviral effects of vitamin D

Громова¹,

Торшин²,

Фролова³

et al. 2020

Medicinskij sovet

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Preventing infectious diseases is very important in obstetric and gynaecological practice. Vitamin D is a complex regulator of innate and adaptive immunity. It is known that lack of vitamin D reduces antibacterial and antiviral immunity, stimulates the development of pathologies associated with chronic systemic inflammation. Evidence from evidence-based medicine indicates the importance of using vitamin D preparations to support immunity. The results of fundamental and clinical studies have shown that chronic inflammation and congenital immunity disorders resulting from vitamin D deficiency significantly reduce the body’s resistance not only to tuberculosis, but also to viral hepatitis, acute respiratory infections, papillomavirus and herpesvirus. In addition to a pronounced antibacterial effect, vitamin D is also characterized by its antiviral action. By increasing the expression of interferon-alpha, cathecidine, defensin and antiviral microRNA, vitamin D activates various mechanisms of congenital antiviral immunity. Studies show the need to compensate for vitamin D deficiency for successful therapy of viral hepatitis, respiratory infections, human papillomavirus (HPV) and herpesvirus. In the present article the molecular fundamentals of antiviral action of vitamin D are sequentially considered, as well as the results of fundamental and clinical studies indicating the action of vitamin D against the viruses of hepatitis, herpes, RSV, Epstein-Barr, human papillomavirus, the possibility of using vitamin D in the treatment of these and other viral pathologies is considered. The authors analyzed data on the effect of vitamin D on immunity functions and antiviral protection of the human body.

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“…Identification and characteristics of the EBV infection in the placenta has been elusive. A few papers argued that the EBV infection is associated with various pathologic conditions during pregnancy, including depression, preeclampsia, and stillbirth ( 7 8 9 ). These findings are mostly thought to be associated with EBV infection of the B lymphocytes; confirmed by polymerase chain reaction (PCR) or serological tests with blood samples which do not involve histopathological information.…”

Section: Introductionmentioning

confidence: 99%

Identification of Epstein-Barr Virus in the Human Placenta and Its Pathologic Characteristics

Kim

Park

et al. 2017

J Korean Med Sci

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Epstein-Barr virus (EBV), a common pathogen in humans, is suspected as the cause of multiple pregnancy-related pathologies including depression, preeclampsia, and stillbirth. Moreover, transmission of EBV through the placenta has been reported. However, the focus of EBV infection within the placenta has remained unknown to date. In this study, we proved the expression of latent EBV genes in the endometrial glandular epithelial cells of the placenta and investigated the cytological characteristics of these cells. Sixty-eight placentas were obtained from pregnant women. Tissue microarray was constructed. EBV latent genes including EBV-encoding RNA-1 (EBER1), Epstein-Barr virus nuclear antigen 1 (EBNA1), late membrane antigen (LMP1), and RPMS1 were detected with silver in situ hybridization and/or mRNA in situ hybridization. Nuclear features of EBV-positive cells in EBV-infected placenta were compared with those of EBV-negative cells via image analysis. Sixteen placentas (23.5%) showed positive expression of all 4 EBV latent genes; only the glandular epithelial cells of the decidua showed EBV gene expression. EBV infection status was not significantly correlated with maternal, fetal, or placental factors. The nuclei of EBV-positive cells were significantly larger, longer, and round-shaped than those of EBV-negative cells regardless of EBV-infection status of the placenta. For the first time, evidence of EBV gene expression has been shown in placental tissues. Furthermore, we have characterized its cytological features, allowing screening of EBV infection through microscopic examination.

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A pre-eclampsia-associated Epstein-Barr virus antibody cross-reacts with placental GPR50

Cited by 8 publications

References 56 publications

A general approach for identifying protein epitopes targeted by antibody repertoires using whole proteomes

A general approach for identifying protein epitopes targeted by antibody repertoires using whole proteomes

About antiviral effects of vitamin D

Identification of Epstein-Barr Virus in the Human Placenta and Its Pathologic Characteristics

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