Development of two potential diagnostic monoclonal antibodies against human cytomegalovirus glycoprotein B

Fan, Jun; Li, Minhuan; Ma, Yuanfang; Huang, Yaping; Liang, Hong‐Qing; Hu, Jianhua; Yao, Hang‐Ping; Ma, Weirui

doi:10.1590/s0100-879x2012007500086

Cited by 6 publications

(8 citation statements)

References 31 publications

(29 reference statements)

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“…A significant correlation between the level of pp65 and gB antigens in the MRC-5 cell line experimentally infected with HCMV has been reported by Jun et al [ 36 ]. It is not unusual to find such correlation among viral proteins as the infection occurs in defined sequences chronologically accompanied by expression of immediate early, early, and late viral antigens.…”

Section: Discussionmentioning

confidence: 75%

Detection of Human Cytomegalovirus in Different Histopathological Types of Glioma in Iraqi Patients

Shamran

Kadhim

Hussain

et al. 2015

BioMed Research International

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Human Cytomegalovirus (HCMV) is an endemic herpes virus that reemerges in cancer patients enhancing oncogenic potential. HCMV infection is associated with certain types of cancer morbidity such as glioblastomas. HCMV, like all other herpes viruses, has the ability to remain latent within the body of the host and can contribute in chronic inflammation. To determine the role of HCMV in glioma pathogenesis, paraffin-embedded blocks from glioma patients (n = 50) and from benign meningioma patients (n = 30) were obtained and evaluated by immunohistochemistry and polymerase chain reaction for the evidence of HCMV antigen expression and the presence of viral DNA. We detected HCMV antigen and DNA for IEI-72, pp65, and late antigen in 33/36, 28/36, and 26/36 in glioblastoma multiforme patients whereas 12/14, 10/14, and 9/14 in anaplastic astrocytoma patients, respectively. Furthermore, 84% of glioma patients were positive for immunoglobulin G (IgG) compared to 72.5% among control samples (P = 0.04). These data indicate the presence of the HCMV virus in a high percentage of glioma samples demonstrating distinct histopathological grades and support previous reports showing the presence of HCMV infection in glioma tissue. These studies demonstrate that detection of low-levels of latent viral infections may play an active role in glioma development and pathogenesis.

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Section: Discussionmentioning

confidence: 75%

Detection of Human Cytomegalovirus in Different Histopathological Types of Glioma in Iraqi Patients

Shamran

Kadhim

Hussain

et al. 2015

BioMed Research International

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“…Wild type residue is bigger. This is probably altering or particularly increasing viral pathogenicity, as, gB gene is one of the most important envelope glycoproteins of HCMV, is implicated in virus entry, cell-to-cell spread, and the fusion of infected cells [43]. The variability and mutations, particularly in gB that arise can be advantageous to the virus resulting in an increase in viral fitness and adaptation [44].…”

Section: Discussionmentioning

confidence: 99%

“…CMV UL55 gene encodes for a glycoprotein B which involved in several essential steps in CMV virus pathogenesis including virus penetration into cells, cell-to-cell spread, and activation of the immune response gB [9] and is involved in the activation of innate immunity as the major antigen for the induction of neutralizing antibodies. gB antibodies have been of interest because of their therapeutic potential for neutralization [10]. Regarding UL55 polymorphism, CMV has been divided into 4 genotypes (gB1-4) [9].…”

Section: Introductionmentioning

confidence: 99%

“…Furthermore detecting gB antigen in patients with HCMV infection may facilitate the monitoring of the infection [10]. Despite advances in viral diagnostic tools in the world, still, there is a difficulty in the diagnosis of CMV virus among transplants in Sudan because it depends on serological tests which has a limited diagnostic value, due to immunosuppressive therapy that causing delayed seroconversion of IgM.…”

Section: Introductionmentioning

confidence: 99%

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Molecular Detection and Glycoprotein B (UL55) Genotyping of Cytomegalovirus among Sudanese Renal Transplant Recipients

Ahmed

Omer

Altyab

2019

Preprint

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Background Cytomegalovirus (CMV) is the most common opportunistic pathogen among solid organ transplant recipients’ especially renal transplants with significant morbidity and mortality. This study was designed to detect CMV DNA and to determine the frequency of different glycoprotein B (UL55) genotypes among Sudanese renal transplant recipients. Methods One hundred and four renal transplant recipients were included in this study. A blood specimen was collected from each recipient. DNA was extracted from plasma using QIAamp DNA mini kit. CMV amplification and quantification (estimation of viral load) was performed using CMV Real – RT Quant kits. Genotyping of Human CMV gB was carried out by nested PCR and sequencing of the highly diverse region of glycoprotein B. Results Cytomegalovirus (CMV) DNA (viremia) was detected in 40/104 (38.5%) of renal transplant recipients. The average of CMV DNA viral load was 358 x104 copies/ml (6.5 log10) ranged from 62 copies/ml (1.8 log 10) to 1.43x108 copies/ml (9 log10). CMV viremia was detected in (60%) of recipients of less than 1-12 months, (17%) of 13-24, (10%) of 25-36, (5%) of 37- 48 and (8%) in more than 48 months post-transplantation with no significant association (P. value = 0.296) between CMV viremia and post renal transplantation time. The association between the type of immunosuppressive drugs and high viral loads (more than 1000 copies /ml) showed a significant difference (P. value =0.05). The correlation between CMV loads of more than 1000 copies/ml and the presence of symptoms of CMV disease were highly significant (P.value =0.00). Fever 7(41%), fever and leucopenia 6(35%) and gastrointestinal disease 4(24%) were the most common presenting symptoms of CMV disease. CMV-genotyping revealed 8 cases (80%) for gB3, and 2 cases (20%) for gB4 genotypes. The most frequent genotype among Sudanese renal transplant recipients was gB3 and no mixed genotypes were observed. Conclusions The frequency of CMV DNA is high among Sudanese renal transplant recipients. CMV viremia viral loads were slightly lower in asymptomatic patients. CMV gB3 is the most predominant glycoprotein B genotype in Sudanese renal transplant recipients.

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“…The scFv2 showed a mean plaque reduction of 68.8% while the mean of plaque reduction for scFv1 and scFv3 were 23.7 and 11.6%, respectively. Although monoclonal antibodies have been produced against human cytomegalovirus gB and gH ( 33 , 34 ), the application of these antibodies in clinical settings is limited due to human anti-mouse antibody (HAMA) response and most of these antibodies have been used for diagnosis purposes. New treatment options for CMV are urgently needed because currently available therapies have major limitations.…”

Section: Discussionmentioning

confidence: 99%

Single Chain Antibodies Against gp55 of Human Cytomegalovirus (HCMV) for Prophylaxis and Treatment of HCMV Infections

Moazen

Ebrahimi

Nejatollahi

2016

Jundishapur J Microbiol

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Background:Immunotherapy is a promising prospective new treatment for cytomegalovirus (CMV) infections. Neutralizing effects have been reported using monoclonal antibodies. Recombinant single chain antibodies (scFvs) due to their advantages over monoclonal antibodies are potential alternatives and provide valuable clinical agents.Objectives:The aim of this study was to select specific single chain antibodies against gp55 of CMV and to evaluate their neutralizing effects. In the present study, we selected specific single chain antibodies against glycoprotein 55 (gp55) of CMV for their use in treatment and diagnosis.Materials and Methods:Single chain antibodies specific against an epitope located in the C-terminal part of gp55 were selected from a phage antibody display library. After four rounds of panning, twenty clones were amplified by the polymerase chain reaction (PCR) and fingerprinted by MvaI restriction enzyme. The reactivities of the specific clones were tested by the enzyme-linked immunosorbent assay (ELISA) and the neutralizing effects were evaluated by the plaque reduction assay.Results:Fingerprinting of selected clones revealed three specific single chain antibodies (scFv1, scFv2 and scFv3) with frequencies 25%, 20 and 20%. The clones produced positive ELISA with the corresponding peptide. The percentages of plaque reduction for scFv1, scFv2 and scFv3 were 23.7, 68.8 and 11.6, respectively.Conclusions:Gp55 of human CMV is considered as an important candidate for immunotherapy. In this study, we selected three specific clones against gp55. The scFvs reacted only with the corresponding peptide in a positive ELISA. The scFv2 with 68.8% neutralizing effect showed the potential to be considered for prophylaxis and treatment of CMV infections, especially in solid organ transplant recipients, for whom treatment of CMV is urgently needed. The scFv2 with neutralizing effect of 68.8%, has the potential to be considered for treatment of these patients. The specific scFv1 and scFv3 with lower neutralizing effects can be used for diagnostic purposes.

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Development of two potential diagnostic monoclonal antibodies against human cytomegalovirus glycoprotein B

Cited by 6 publications

References 31 publications

Detection of Human Cytomegalovirus in Different Histopathological Types of Glioma in Iraqi Patients

Detection of Human Cytomegalovirus in Different Histopathological Types of Glioma in Iraqi Patients

Molecular Detection and Glycoprotein B (UL55) Genotyping of Cytomegalovirus among Sudanese Renal Transplant Recipients

Single Chain Antibodies Against gp55 of Human Cytomegalovirus (HCMV) for Prophylaxis and Treatment of HCMV Infections

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