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1

Hinderer, Walter, Dieter Lang, Markus Rothe, Rolf Vornhagen, Hans H. Sonneborn, and Hans Wolf. "Serodiagnosis of Epstein-Barr Virus Infection by Using Recombinant Viral Capsid Antigen Fragments and Autologous Gene Fusion." Journal of Clinical Microbiology 37, no. 10 (1999): 3239–44. http://dx.doi.org/10.1128/jcm.37.10.3239-3244.1999.

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Using recombinant 15- to 30-kDa fragments and fusion with glutathione S-transferase (GST), we investigated the seroreactivity of three large structural proteins of Epstein-Barr virus (EBV), p150 (BcLF1, capsid), p143 (BNRF1, tegument), and gp125 (BALF4, membrane) in Western blots. None of 13 fragments tested, however, was qualified for diagnostic application. In contrast, the two small viral capsid antigens (VCA), p18 (BFRF3) and p23 (BLRF2), demonstrated sensitive (100%) EBV-specific immunoglobulin G (IgG) reactivities. While p18 additionally showed maximum sensitivity for IgM detection, the IgM sensitivity of p23 was restricted (44%). An autologous fusion protein, p23-p18, which consists N-terminally of full-length p23, followed by the carboxy half of p18, was constructed. This antigen was subjected to indirect VCA enzyme-linked immunosorbent assays (ELISAs), for IgG and IgM, as well as to a μ-capture (μc) IgM ELISA. All assays were found to be 100% specific when EBV-negative sera were tested. Using sera from previously infected individuals, the p23-p18 fusion revealed an improved IgG sensitivity of 99% compared to sensitivities of 97 and 93% for the single antigens p18 and p23, respectively. The sensitivity and specificity of the indirect IgM ELISA with samples of primary and past infections, respectively, were 100%. The μc principle for IgM overcame completely the interference by rheumatoid factors. Compared to the specificity of the indirect IgM version, the specificity with sera collected from rheumatoid arthritis patients increased from 48 to 100%. In summary, the p23-p18 IgG and μc IgM ELISAs showed excellent performances and are promising new diagnostic tests for the detection of EBV-specific antiviral capsid antibodies.
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2

Niraula, S., Y. S. Zong, L. Z. Zhai, C. C. Guo, and T. Y. Lin. "Investigation on the serum antibodies levels against Epstein-Barr virus in pulmonary lymphoepithelioma-like carcinoma." Journal of Clinical Oncology 25, no. 18_suppl (June 20, 2007): 18186. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.18186.

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18186 Background: Pulmonary lymphoepithelioma-like carcinoma (PLELC) belongs to large cell sub-type of non-small cell lung cancer (NSCLC) with just about 160 cases reported previously. Its epidemiology, prognosis and therapeutic approach is evidently different from other NSCLCs. EBV infection is seen in 100% of Asian PLELC patients whenever tested. The aim of this study was to analyze serum antibodies level against EBV in PLELC patients. Methods: Sera of all seven patients with re-confirmed PLELC from a single institute in Canton, China in the past 4 years were collected. Serum levels of 8 different antibodies against EBV (Epstein-Barr virus): EBNA1 (EBV nuclear antigen 1- IgA and IgG), Zta (Bam Z transactivator antigen-IgA and IgG), VCA-p18 (Viral capsid antigen-p18-IgA and IgG), VCA-antigen complex (VCA-IgA) and Early antigen complex (EA-IgA ) were measured in each of these patients using enzyme-linked immunosorbent assay and Immunoenzymatic assay respectively. Results: Out of 7 cases, 6 showed high EBNA-1 level, 4 showed high zta, 3 showed high VCA-p18, 3 showed high titer of VCA complex and 2 showed high EA complex titer ( Table 1 ) Conclusions: Though small sample size, this is the first study in this depth ever to conclude that sera of all Asian patients with pulmonary LELC have high antibody titers against EBV. The infection mainly is latency II type as seen in Nasopharyngeal carcinoma and Hodgkin’s disease as well. A small portion of PLELC express lytic products such as Zta, EA and VCA. The authors assume that pre-therapeutic measurement of serum levels of anti-EBV antibodies (at least 2 kinds) is highly warranted in suspected Asian NSCLC patients. Positive result strongly puts PLELC into differential diagnosis. [Table: see text] No significant financial relationships to disclose.
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Tranchand-Bunel, D., C. Auriault, E. Diesis, and H. Gras-Masse. "Detection of human antibodies using “convergent” combinatorial peptide libraries or “mixotopes” designed from a nonvariable antigen: Application to the EBV viral capsid antigen p18." Journal of Peptide Research 52, no. 6 (January 12, 2009): 495–508. http://dx.doi.org/10.1111/j.1399-3011.1998.tb01254.x.

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4

Ogolla, Sidney, Ibrahim I. Daud, Amolo S. Asito, Odada P. Sumba, Collins Ouma, John Vulule, Jaap M. Middeldorp, Arlene E. Dent, Saurabh Mehta, and Rosemary Rochford. "Reduced Transplacental Transfer of a Subset of Epstein-Barr Virus-Specific Antibodies to Neonates of Mothers Infected with Plasmodium falciparum Malaria during Pregnancy." Clinical and Vaccine Immunology 22, no. 11 (September 16, 2015): 1197–205. http://dx.doi.org/10.1128/cvi.00270-15.

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ABSTRACTOver 35% of children in a region of malaria endemicity are infected with Epstein-Barr virus (EBV) by 6 months of age. This susceptibility may be linked to impaired transplacental transfer of antibodies. In this study, we determined the effect of malaria exposure during pregnancy on the transfer of EBV-specific maternal antibodies in a region of western Kenya that experiences endemic malaria. Pregnant mothers were recruited and followed up until delivery to determine levels of neonatal malaria exposure. Levels of EBV lytic (viral capsid antigen [VCA], Z transcriptional activator [Zta], and early diffuse antigen complex [EAd]) and EBV latent (EBV nuclear antigen-1 (EBNA1]) and tetanus-specific IgG antibodies were measured in 70 paired maternal and cord blood samples using a Luminex-bead-based assay. A high proportion (63%) of the infants were exposed to malariain utero. Levels of EBV- and tetanus-specific antibodies were similar in malaria-infected mothers and in mothers who had no detectable malaria infection. Malaria-exposed neonates had significantly lower levels of anti-EBNA1, anti-Zta, and anti-EAd antibodies than were seen in their mothers.In uteromalaria exposure resulted in significant reductions in transplacental transfer of anti-VCA-p18 and anti-EBNA1 antibodies of 13% and 22%, respectively. Neonates received significantly low levels of anti-Zta and anti-EAd antibodies irrespective of malaria exposure levels. In multivariate analysis,in uteromalaria exposure was associated with a significant reduction in the transfer of anti-VCA-p18 and anti-EBNA1 antibodies to the neonates (P= 0.0234 andP= 0.0017, respectively). Malaria during pregnancy results in differential levels of transfer of EBV-specific antibodies from the mother to the fetus. The impaired transplacental transfer of some antibodies may lead to the malaria-exposed neonates being susceptible to early EBV infection.
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5

Paramita, Dewi K., Jajah Fachiroh, Sofia M. Haryana, and Jaap M. Middeldorp. "Two-Step Epstein-Barr Virus Immunoglobulin A Enzyme-Linked Immunosorbent Assay System for Serological Screening and Confirmation of Nasopharyngeal Carcinoma." Clinical and Vaccine Immunology 16, no. 5 (March 25, 2009): 706–11. http://dx.doi.org/10.1128/cvi.00425-08.

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ABSTRACT Undifferentiated nasopharyngeal carcinoma (NPC; WHO type III) is 100% associated with Epstein-Barr virus (EBV) infection and the fourth most prevalent cancer in Indonesian males. Therapy failure is high, since most patients come to the hospital at an advanced stage of disease. Screening for early-stage NPC is needed. Here, a simple and economical two-step enzyme-linked immunosorbent assay (ELISA) system is proposed for diagnosing NPC in high-risk populations, employing the peptide-based immunoglobulin A (IgA) EBNA1 plus viral capsid antigen p18 ELISA as an initial screening test and the IgA early antigen (EA) ELISA using a different set of EBV antigens as a confirmation test. A total of 151 NPC patients and 199 regional healthy EBV carriers were used to evaluate the two-step ELISA approach. Routinely, EBV IgG immunoblotting is used as a standard confirmation test. The sensitivity and specificity for diagnosing NPC by the two-step ELISA approach increased from 85.4% to 96.7% and 90.1% to 98%, respectively, with positive predictive values and negative predictive values increasing from 78.7 and 93.9% to 97.3 and 97.5%, respectively, relative to the immunoblotting confirmation system. On discrepant samples, additional testing was done by EBV DNA load quantification in blood. Results showed that 5/11 discrepant NPC samples with an elevated IgA EA ELISA also had elevated an EBV DNA load in the circulation (range, 3,200 to 25,820 copies/ml). Therefore, the IgA EA ELISA is proposed as a confirmation test in first-line NPC serological screening studies. This two-step EBV ELISA system provides a standardized approach for NPC screening and may be used in combination with dried blood sampling in future field studies for identification of early-stage NPC in high-risk regions.
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6

Dias, Michelle H. F., Luiz F. F. Guimarães, Matheus G. Barcelos, Eduardo U. M. Moreira, Maria F. A. do Nascimento, Taís N. de Souza, Camilla V. Pires, et al. "Impact of Epstein-Barr virus co-infection on natural acquired Plasmodium vivax antibody response." PLOS Neglected Tropical Diseases 16, no. 8 (August 3, 2022): e0010305. http://dx.doi.org/10.1371/journal.pntd.0010305.

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Background The simultaneous infection of Plasmodium falciparum and Epstein-Barr virus (EBV) could promote the development of the aggressive endemic Burkitt’s Lymphoma (eBL) in children living in P. falciparum holoendemic areas. While it is well-established that eBL is not related to other human malaria parasites, the impact of EBV infection on the generation of human malaria immunity remains largely unexplored. Considering that this highly prevalent herpesvirus establishes a lifelong persistent infection on B-cells with possible influence on malaria immunity, we hypothesized that EBV co-infection could have impact on the naturally acquired antibody responses to P. vivax, the most widespread human malaria parasite. Methodology/Principal findings The study design involved three cross-sectional surveys at six-month intervals (baseline, 6 and 12 months) among long-term P. vivax exposed individuals living in the Amazon rainforest. The approach focused on a group of malaria-exposed individuals whose EBV-DNA (amplification of balf-5 gene) was persistently detected in the peripheral blood (PersVDNA, n = 27), and an age-matched malaria-exposed group whose EBV-DNA could never be detected during the follow-up (NegVDNA, n = 29). During the follow-up period, the serological detection of EBV antibodies to lytic/ latent viral antigens showed that IgG antibodies to viral capsid antigen (VCA-p18) were significantly different between groups (PersVDNA > NegVDNA). A panel of blood-stage P. vivax antigens covering a wide range of immunogenicity confirmed that in general PersVDNA group showed low levels of antibodies as compared with NegVDNA. Interestingly, more significant differences were observed to a novel DBPII immunogen, named DEKnull-2, which has been associated with long-term neutralizing antibody response. Differences between groups were less pronounced with blood-stage antigens (such as MSP1-19) whose levels can fluctuate according to malaria transmission. Conclusions/Significance In a proof-of-concept study we provide evidence that a persistent detection of EBV-DNA in peripheral blood of adults in a P. vivax semi-immune population may impact the long-term immune response to major malaria vaccine candidates.
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7

Herdini, Camelia, Susanna Hutajulu, Sagung Rai Indrasari, Bambang Hariwiyanto, Jajah Fachiro, Sofia Mubarika, and Jaap Middeldorp. "Uji serologi IgA karakter KNF EBNA1+VCA p-18 pada penderita keluhan kronis kepala leher." Oto Rhino Laryngologica Indonesiana 41, no. 2 (December 1, 2011): 105. http://dx.doi.org/10.32637/orli.v41i2.46.

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Background: Nasopharyngeal carcinoma (NPC), especially the WHO type III, is correlated almost100% with Epstein Barr Virus (EBV) infection. This is indicated by high IgG and IgA antibody responsesagainst viral capsid antigen (VCA), early antigen (EA) and Epstein Barr Nuclear antigen (EBNA).Increased IgA NPC character antibodies may be detected 2-10 years before the presence of the tumor. Thisoccurs as a result of reactivation of EBV infection. Purpose: To find out the level of IgA NPC characterantibodies (EBNA1+VCA p-18) in patients with chronic symptoms in the head and neck and to determine whether the level of IgA can be used as an early sign of NPC. Methods: Observational analytic study on 218 patients with chronic symptoms in the head and neck. The research was conducted from July 2006to September 2010. ELISA technique was used as serology test for IgA (EBNA1+VCA p-18). Result: Samples were 90 males and 128 females. High level of IgA by ELISA was found in 28 males (31.1%) and 45 females (35.2%). The IgA level tended to increase with age. The most common chronic symptoms inthe head and neck were chronic rhinitis (15.6%) and nasal obstruction (7.8%). From all patients who hadhigh level of IgA, 3 patients (4.1%) were found positive of early stage NPC. Conclusion: More than 33%of patients with chronic symptoms of head and neck had high level of IgA NPC character. This methodcan be used as an early detection of NPC. Keywords: serology test in NPC, EBNA1, VCA p-18, NPC symptoms in head and neck Abstrak : Latar belakang: Karsinoma nasofaring (KNF) terutama tipe WHO III berkorelasi hampir 100%dengan infeksi Epstein Barr Virus (EBV). Hal ini ditunjukkan dengan tingginya respons antibodi IgGdan IgA terhadap viral capsid antigen (VCA), early antigen (EA) EBV serta antibodi Epstein BarrNuclear Antigen (EBNA). Kenaikan antibodi IgA dengan karakter KNF dapat terjadi 2-10 tahun sebelumterjadinya tumor. Hal ini terjadi sebagai akibat adanya reaktivasi infeksi EBV. Tujuan: Mengetahui kadarIgA karakter KNF (EBNA1+VCA p-18) pada penderita dengan gejala kronis di daerah kepala dan leherdan mengetahui apakah kadar IgA dapat digunakan sebagai tanda awal terjadinya KNF. Metode: Suatukajian analitik observasional terhadap 218 penderita dengan gejala kronis di daerah kepala dan leher.Penelitian ini dilakukan Juli 2006 sampai dengan September 2010. Pemeriksaan serologi IgA (EBNA1+VCA-p18)dilakukan denganteknik ELISA.Hasil:Terdapat90penderita laki-lakidan128 penderitaperempuan.HasiltesserologiIgAELISAdengankadartinggiditemukanpada28laki-laki(31,1%)dan45perempuan (35,2%). Kadar IgA cenderung meningkat pada peningkatan usia. Gejala kronis yangterbanyak dikeluhkan penderita adalah rinitis kronis, yaitu sebanyak 34 penderita (15,6%), diikuti denganobstruksi hidung sebanyak 17 penderita (7,8%). Pemeriksaan klinis lebih lanjut dari penderita yangmempunyai kadar IgA tinggi menunjukkan bahwa 3 penderita (4,1%) positif terkena kanker nasofaringstadium awal. __ Lebih dari 33% penderita dengan gejala kronis di daerah kepala dan lehermemiliki kadar IgA karakter KNF yang tinggi. Kadar IgA karakter KNF yang tinggi dapat digunakansebagai penanda awal kejadian KNF. Kata kunci: uji serologi KNF,EBNA1, VCA p-18, gejala KNF
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8

Fachiroh, J., D. K. Paramita, B. Hariwiyanto, A. Harijadi, H. L. Dahlia, S. R. Indrasari, H. Kusumo, et al. "Single-Assay Combination of Epstein-Barr Virus (EBV) EBNA1- and Viral Capsid Antigen-p18-Derived Synthetic Peptides for Measuring Anti-EBV Immunoglobulin G (IgG) and IgA Antibody Levels in Sera from Nasopharyngeal Carcinoma Patients: Options for Field Screening." Journal of Clinical Microbiology 44, no. 4 (April 1, 2006): 1459–67. http://dx.doi.org/10.1128/jcm.44.4.1459-1467.2006.

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9

Xue, Ning, Shan Xing, Weiguo Ma, Jiahe Sheng, Zhiliang Huang, and Qingxia Xu. "Combination of Plasma MIF and VCA-IgA Improves the Diagnostic Specificity for Patients With Nasopharyngeal Carcinoma." Technology in Cancer Research & Treatment 19 (January 1, 2020): 153303382093577. http://dx.doi.org/10.1177/1533033820935773.

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Introduction: The purpose of this study is to evaluate the diagnostic value of macrophage migration inhibitory factor in patients with nasopharyngeal carcinoma. Materials and Methods: The expression levels of macrophage migration inhibitory factor in nasopharyngeal carcinoma cell lines, tumor tissues, and plasma were measured by real-time polymerase chain reaction, Western blotting, enzyme-linked immunosorbent assay, and immunohistochemistry. Plasma Epstein-Barr virus viral capsid antigen was determined by immunoenzymatic techniques. Results: Both the messenger RNA and protein expression levels of macrophage migration inhibitory factor were upregulated in nasopharyngeal carcinoma cell lines and nasopharyngeal carcinoma tissues. Macrophage migration inhibitory factor in plasma was significantly elevated in patients with nasopharyngeal carcinoma compared to Epstein-Barr virus viral capsid antigen–negative and Epstein-Barr virus viral capsid antigen–positive healthy donors. The combination of macrophage migration inhibitory factor and Epstein-Barr virus viral capsid antigen was better for diagnosing nasopharyngeal carcinoma (area under receiver operating characteristic curve = 0.925, 95% CI: 0.898-0.951) than macrophage migration inhibitory factor (area under receiver operating characteristic curve = 0.778, 95% CI: 0.732-0.824) and Epstein-Barr virus viral capsid antigen. Combining macrophage migration inhibitory factor and Epstein-Barr virus viral capsid antigen had higher specificity (82.40% vs 69.96%) and higher positive predictive value (79.17% vs 67.44%) without an obvious reduction in sensitivity (95.25%) compared to Epstein-Barr virus viral capsid antigen alone. Macrophage migration inhibitory factor was highly expressed in nasopharyngeal carcinoma cell lines, whereas it was not associated with Epstein-Barr virus infection. The level of macrophage migration inhibitory factor in plasma was not related to the titer of Epstein-Barr virus viral capsid antigen. Conclusion: The combination of macrophage migration inhibitory factor and Epstein-Barr virus viral capsid antigen increases the specificity and positive predictive value of detecting nasopharyngeal carcinoma and improves the diagnostic accuracy of nasopharyngeal carcinoma in high-risk individuals.
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Lee, Sook-Kyung, Kunio Nagashima, and Wei-Shau Hu. "Cooperative Effect of Gag Proteins p12 and Capsid during Early Events of Murine Leukemia Virus Replication." Journal of Virology 79, no. 7 (April 1, 2005): 4159–69. http://dx.doi.org/10.1128/jvi.79.7.4159-4169.2005.

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ABSTRACT The Gag polyprotein of murine leukemia virus (MLV) is processed into matrix (MA), p12, capsid (CA), and nucleocapsid (NC) proteins. p12 affects early events of virus replication and contains a PPPY motif important for virus release. To probe the functions of p12 in the early steps of MLV replication, we tested whether p12 can be replaced by spleen necrosis virus (SNV) p18, human immunodeficiency virus type 1 p6, or Rous sarcoma virus p2b. Analyses revealed that all chimeras generated virions at levels similar to that of MLV gag-pol; however, none of them could support MLV vector replication, and all of them exhibited severely reduced DNA synthesis upon virus infection. Because a previously reported SNV gag-MLV pol chimera, but not the MLV hybrid with SNV p18, can support replication of an MLV vector, we hypothesized that other Gag proteins act cooperatively with p12 during the early phase of virus replication. To test this hypothesis, we generated three more MLV-based chimeras containing SNV CA, p18-CA, or p18-CA-NC. We found that the MLV chimera containing SNV p18-CA or p18-CA-NC could support MLV vector replication, but the chimera containing SNV CA could not. Furthermore, viruses derived from the MLV chimera with SNV CA could synthesize viral DNA upon infection but were blocked at a post-reverse-transcription step and generated very little two long terminal repeat circle DNA, thereby producing a phenotype similar to that of the provirus formation-defective p12 mutants. Taken together, our data indicate that when p12/p18 or CA was from different viruses, despite abundant virus production and proper Gag processing, the resulting viruses were not infectious. However, when p12/p18 and CA were from the same virus, even though they were from SNV and not MLV, the resulting viruses were infectious. Therefore, these results suggest a cooperative effect of p12 and CA during the early events of MLV replication.
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Storset, A. K., Ø. Evensen, and E. Rimstad. "Immunohistochemical Identification of Caprine Arthritis-Encephalitis Virus in Paraffin-embedded Specimens from Naturally Infected Goats." Veterinary Pathology 34, no. 3 (May 1997): 180–88. http://dx.doi.org/10.1177/030098589703400302.

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The expression of caprine arthritis-encephalitis virus capsid protein was studied in seropositive naturally infected asymptomatic goats (10), seropositive naturally infected encephalitic kids (12) and goats (4), and noninfected control goats (3). Rabbit antiserum to recombinant viral capsid and matrix proteins were used in a biotin-streptavidin-alkaline phosphatase complex immunohistochemical method on sections of formalin-and ethanol-fixed tissue specimens. Macrophages in inflamed areas of the lung (8/12), in the brain (5/16), and in the spinal cord (4/16) from encephalitic animals harbored viral antigens, as revealed by immunohistochemistry and use of a capsid protein-specific antiserum. Altogether 12/16 encephalitic animals tested positive for viral antigen. Viral antigens were found in 5/10 seropositive asymptomatic goats in macrophages located in the lung (3), the udder (1), and the medulla of lymph nodes (4). None of the control animals tested positive for viral antigen. Ethanol fixation showed highest sensitivity, and the lowest antigen concentration that revealed a positive signal discernible from background was twofold higher in ethanol-fixed specimens than in formalin-fixed specimens. The evaluation was performed on artificial antigen substrates embedded with defined concentrations of recombinant viral capsid protein. Immunohistochemistry is a valuable supplement to the methods presently available for diagnosis in cases suspicious of caprine arthritis-encephalitis.
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Kim, H. J., J. Y. Lee, H. A. Kang, Y. Lee, E. J. Park, and H. J. Kim. "Oral immunization with whole yeast producing viral capsid antigen provokes a stronger humoral immune response than purified viral capsid antigen." Letters in Applied Microbiology 58, no. 3 (November 19, 2013): 285–91. http://dx.doi.org/10.1111/lam.12188.

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13

Radhakrishnan, Sujatha, Jennifer Gordon, Luis Del Valle, Jianqi Cui, and Kamel Khalili. "Intracellular Approach for Blocking JC Virus Gene Expression by Using RNA Interference during Viral Infection." Journal of Virology 78, no. 13 (July 1, 2004): 7264–69. http://dx.doi.org/10.1128/jvi.78.13.7264-7269.2004.

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ABSTRACT The human polyomavirus, JC virus (JCV), encodes two regulatory proteins at the early (T antigen) and the late (agnoprotein) phases of viral infection whose activities are important for the production of the viral capsid proteins and the dysregulation of several host factors and their functions. For this study, we designed and utilized an RNA interference strategy via small interfering RNAs (siRNAs) that targeted the expression of T antigen and agnoprotein in human astrocytic cells. The treatment of cells with specific siRNA oligonucleotides targeting a conserved region of T antigen, nucleotides (nt) 4256 to 4276 (Mad-1 strain), caused a >50% decline in the level of T antigen and in its transcriptional activity upon the viral capsid genes as well as a significant reduction in viral DNA replication in infected cells. Similarly, a single siRNA that aimed at nt 324 to 342 of agnoprotein noticeably reduced early and late viral protein production. A combined treatment of the infected cells with both T-antigen and agnoprotein siRNAs completely abolished viral capsid protein production, indicative of the ability of the siRNAs to effectively halt multiplication of the virus in infected cells. These observations provide a new avenue for possible treatments of patients with the JCV-induced demyelinating disease progressive multifocal leukoencephalopathy.
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Verma, Dinesh, Jacob Thompson, and Sankar Swaminathan. "Spironolactone blocks Epstein–Barr virus production by inhibiting EBV SM protein function." Proceedings of the National Academy of Sciences 113, no. 13 (March 14, 2016): 3609–14. http://dx.doi.org/10.1073/pnas.1523686113.

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Clinically available drugs active against Epstein–Barr virus (EBV) and other human herpesviruses are limited to those targeting viral DNA replication. To identify compounds directed against other steps in the viral life cycle, we searched for drugs active against the EBV SM protein, which is essential for infectious virus production. SM has a highly gene-specific mode of action and preferentially enhances expression of several late lytic cycle EBV genes. Here we demonstrate that spironolactone, a mineralocorticoid receptor antagonist approved for clinical use, inhibits SM function and infectious EBV production. Expression of EBV viral capsid antigen is highly SM dependent, and spironolactone inhibits viral capsid antigen synthesis and capsid formation, blocking EBV virion production at a step subsequent to viral DNA replication. In addition, spironolactone inhibits expression of other SM-dependent genes necessary for infectious virion formation. We further demonstrate that molecules structurally related to spironolactone with similar antimineralocorticoid blocking activity do not inhibit EBV production. These findings pave the way for development of antiherpesvirus drugs with new mechanisms of action directed against SM and homologous essential proteins in other herpesviruses.
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Larsen, P. D., L. C. Bloomer, and P. F. Bray. "Epstein-Barr nuclear antigen and viral capsid antigen antibody titers in multiple sclerosis." Neurology 35, no. 3 (March 1, 1985): 435. http://dx.doi.org/10.1212/wnl.35.3.435.

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Grandjean Lapierre, Simon, Emilie Vallières, Leila Rabaamad, Manon Labrecque, Caroline Chartrand, and Christian Renaud. "Evaluation of the abbot Architect™ epstein-barr virus viral capsid antigen IgM, viral capsid antigen IgG and nuclear antigen IgG assays in a pediatric and adult population." Journal of Clinical Virology 81 (August 2016): 1–5. http://dx.doi.org/10.1016/j.jcv.2016.05.008.

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Feng, Zhenru, Zhiyan Li, Baohuan Sui, Guobing Xu, and Tiean Xia. "Serological diagnosis of infectious mononucleosis by chemiluminescent immunoassay using capsid antigen p18 of Epstein-Barr virus." Clinica Chimica Acta 354, no. 1-2 (April 2005): 77–82. http://dx.doi.org/10.1016/j.cccn.2004.11.010.

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Gu, Linlin, Mert Icyuz, Valentina Krendelchtchikova, Alexandre Krendelchtchikov, Alison E. Johnston, and Qiana L. Matthews. "Development of an Ad5H3 Chimera Using the “Antigen Capsid-Incorporation” Strategy for an Alternative Vaccination Approach." Open Virology Journal 10, no. 1 (April 26, 2016): 10–20. http://dx.doi.org/10.2174/1874357901610010010.

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Background:Adenovirus type 5 (Ad5) achieved success as a conventional transgene vaccine vector in preclinical trials, however; achieved poor efficiency in some of the clinical trials, due to the major hurdle associated with Ad5 pre-existing immunity (PEI) in the majority of the human population.Objective:We sought to generate Ad5-based chimeras to assess their capabilities to bypass this bottleneck and to induce antigen-specific humoral immune response.Methods:A His6tag was incorporated into the hypervariable region 2 (HVR2) of hexon3 (H3) capsid protein using the “Antigen Capsid-Incorporation” strategy. This lead to the construction of a viral chimera, Ad5H3-HVR2-His. Ad5H3 was generated previously by substituting the hexon of Ad5 (hexon5) with the hexon from adenovirus type 3 (Ad3).Results:His6was presented on the viral capsid surface and recognized by a His6antibody. Anin vitroneutralization assay with Ad5 sera indicated the ability of Ad5 chimeras to partially escape Ad5 immunity. Immunization with Ad5H3-HVR2-His generated significant humoral response to the incorporated tagged peptide, when compared to the immunizations with controls.Conclusion:Based on ourin vitrostudies the data suggested that Ad5H3 as a novel chimeric vaccine platform yields the possibility to escape Ad5 neutralization, and the potential to generate robust humoral immunity against incorporated antigens using the “Antigen Capsid-Incorporation” strategy.
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Hui, Daniel J., Etiena Basner-Tschakarjan, Gary C. Pien, William D. Martin, Annie S. DeGroot, Katherine A. High, and Federico Mingozzi. "Peptide-Induced Antigen-Specific CD4+CD25+FoxP3+ T Cells Suppress Cytotoxicity T Cell Responses Directed Against the AAV Capsid." Blood 116, no. 21 (November 19, 2010): 3769. http://dx.doi.org/10.1182/blood.v116.21.3769.3769.

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Abstract Abstract 3769 Recent advances in adeno-associated viral (AAV) vector-mediated gene transfer continue to offer hope for the correction of monogenic disorders such as hemophilia B. However, unanticipated T cell responses directed against viral capsid epitopes may limit the efficacy of AAV gene transfer. A phase I clinical study in which an AAV2 vector expressing human factor IX (FIX) was delivered systemically provided the first evidence that AAV vector administration at high doses may trigger the expansion of memory CD8+ T cells directed against AAV capsid epitopes. This response was associated with the loss of FIX transgene expression and a transient increase in liver enzymes. Additional studies in human subjects undergoing AAV gene transfer suggest that the capsid antigen load is an important determinant of capsid-specific T cell activation. Thus, strategies for the modulation of capsid T cell responses could contribute to achieving sustained transgene expression following high dose delivery of AAV. MHC class II peptide ligands identified within the human IgG Fc fragment (Tregitopes, Blood 2008;112:3303) have been shown to expand regulatory T cells (Tregs). Restimulation of human peripheral blood mononuclear cells (PBMC) in vitro with AAV capsid antigen in the presence of Tregitopes resulted in the suppression of capsid-specific CD8+ T cells and in the expansion of CD4+CD25+FoxP3+ Tregs. To better define the nature of Tregitope-induced Tregs, we depleted CD25+ cells from PBMC prior to in vitro restimulation. This completely prevented capsid-specific CTL suppression and the expansion of Tregs, suggesting that Tregitopes act by expanding natural Tregs. Cytokine ELISA on conditioned media from PBMC co-cultured with AAV antigen and Tregitopes showed a 50% decrease in IL-2 levels and a >500-fold increase in IL-10 levels. These results suggest that the effect of Tregitopes may be cytokine mediated. To test this hypothesis, we used a transwell system in which the CD4+ T cell fraction of Tregitope-restimulated PBMC was co-cultured with the capsid-specific CD8+ T cells. Without cell contact, a nearly 50% suppression of anti-capsid CD8+ T cell responses was observed. Further evidence supporting the role of cytokine-mediated suppression came from the observation that Tregitope-treated capsid-specific CD8+ T cells appeared to be anergic, and depletion of CD4+ T cells (Tregs) followed by a 24-hour incubation of CD8+CD4− T cells with IL-2 restored >80% of CTL activity. Finally, antigen specificity of Tregitope-induced Tregs was tested by expanding PBMC in vitro with HLA-B*0702-restricted epitopes from either the AAV capsid or the Epstein-Barr Virus (EBV). After in vitro restimulation, negatively-isolated CD4+ T cells expanded in the presence of EBV antigen and Tregitopes were co-incubated with either CD8+ T cells expanded against the AAV capsid or against EBV. Suppression of CTL activity was observed only when EBV Tregs were co-incubated with EBV CD8+ T cells. Similarly, Tregs isolated from AAV and Tregitope cultures suppressed AAV-specific CD8+ T cells but not EBV-specific CD8+T cells. These results suggest that inhibition of CD8+ T cell responses is antigen-specific. We conclude that Tregitopes induce the expansion of Tregs, which can mediate a potent antigen-specific inhibition of CD8+ T cell responses directed to the AAV capsid. Disclosures: Hui: Children's Hospital of Philadelphia: Patents & Royalties. Martin:EpiVax: Employment, Equity Ownership, Patents & Royalties. DeGroot:EpiVax: Employment, Equity Ownership. High:Children's Hospital of Philadelphia: Patents & Royalties. Mingozzi:Children's Hospital of Philadelphia: Patents & Royalties.
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Tranchand-Bunel, D., H. Gras-Masse, B. Bourez, L. Dedecker, and C. Auriault. "Evaluation of an Epstein-Barr Virus (EBV) Immunoglobulin M Enzyme-Linked Immunosorbent Assay Using a Synthetic Convergent Peptide Library, or Mixotope, for Diagnosis of Primary EBV Infection." Journal of Clinical Microbiology 37, no. 7 (1999): 2366–68. http://dx.doi.org/10.1128/jcm.37.7.2366-2368.1999.

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An immunoglobulin M (IgM) enzyme-linked immunosorbent assay (ELISA) was developed by using a 24-amino-acid peptide of the 18-kDa Epstein-Barr virus (EBV) viral capsid antigen (VCAp18). IgM detection was increased by 23% by using this antigen. Detection of IgM antibodies to the EBV proteins in the new ELISA was 100% specific and 95% sensitive.
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Esterling, B. A., M. H. Antoni, M. Kumar, and N. Schneiderman. "Emotional repression, stress disclosure responses, and Epstein-Barr viral capsid antigen titers." Psychosomatic Medicine 52, no. 4 (July 1990): 397–410. http://dx.doi.org/10.1097/00006842-199007000-00002.

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22

Mazur, Carlos, Jenner K. P. Reis, Romulo C. Leite, Maria das Graças M. Danelli, Mitika K. Hagiwara, Ana Carolina M. A. de Góes, and Marcos A. Medeiros. "Evaluation of a recombinant p24 antigen for the detection of Feline Immunodeficiency Virus-specific antibodies." Pesquisa Veterinária Brasileira 30, no. 10 (October 2010): 877–80. http://dx.doi.org/10.1590/s0100-736x2010001000011.

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Feline Immunodeficiency Virus is a worldwide infection and is considered a significant pathogen. The diagnosis of FIV infections is mainly based on commercially available rapid tests that are highly expensive in Brazil, hence it is rarely performed in the country. Furthermore, lentiviruses grow slowly and poorly in tissue cultures, making the production of viral antigen by classic means and thus the establishment of FIV immunodiagnosis impracticable. In order to deal with this, recombinant DNA techniques were adopted to produce the protein p24, a viral capsid antigen. The protein's reactivity evaluation analyzed by Western blot indicated that this recombinant antigen can be a useful tool for the immunodiagnostic of FIV infections.
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Jahan, Jasmine Akhter, S. M. Rashed Ul Islam, Md Shafikul Alam Tanim, Tasnim Binte Ahmed, Md Rabiul Alam, and Ferdousy Begum. "Analysis of the association between Epstein Barr virus infection and Hodgkin lymphoma." Bangabandhu Sheikh Mujib Medical University Journal 15, no. 4 (February 5, 2023): 32–36. http://dx.doi.org/10.3329/bsmmuj.v15i4.64225.

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Epstein Barr virus plays an important role in the pathogenesis of Hodgkin lymphoma. However, the frequency of its association in Bangladeshi people has not been widely studied. The aim of this study was to determine the association of Epstein Barr virus association in Hodgkin Lymphoma through detection of Latent Membrane Protein 1 by immunohistochemistry and serum Epstein Barr virus viral capsid antigen IgG antibody titer by serology. This was a cross-sectional study in purposively selected 45 histologically diagnosed cases of Hodgkin lymphoma at Bangabandhu Sheikh Mujib Medical University, Dhaka, during the period of March 2017 to December 2018. Latent membrane protein 1 was positive in 71.1% of cases of Hodgkin lymphoma. Among these positive cases, 96% of cases had significantly raised titer of serum Epstein Barr virus viral capsid antigen IgG antibody (P<0.0001 obtained by Fisher’s Exact test), which had a male predominance. Mixed cellularity classical Hodgkin lymphoma showed the highest positivity. Bangabandhu Sheikh Mujib Medical University Journal 2022;15(4):32-36
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Aves, Kara-Lee, Louise Goksøyr, and Adam F. Sander. "Advantages and Prospects of Tag/Catcher Mediated Antigen Display on Capsid-Like Particle-Based Vaccines." Viruses 12, no. 2 (February 6, 2020): 185. http://dx.doi.org/10.3390/v12020185.

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Capsid-like particles (CLPs) are multimeric, repetitive assemblies of recombinant viral capsid proteins, which are highly immunogenic due to their structural similarity to wild-type viruses. CLPs can be used as molecular scaffolds to enable the presentation of soluble vaccine antigens in a similar structural format, which can significantly increase the immunogenicity of the antigen. CLP-based antigen display can be obtained by various genetic and modular conjugation methods. However, these vary in their versatility as well as efficiency in achieving an immunogenic antigen display. Here, we make a comparative review of the major CLP-based antigen display technologies. The Tag/Catcher-AP205 platform is highlighted as a particularly versatile and efficient technology that offers new qualitative and practical advantages in designing modular CLP vaccines. Finally, we discuss how split-protein Tag/Catcher conjugation systems can help to further propagate and enhance modular CLP vaccine designs.
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25

Preziuso, S., GE Magi, S. Mari, and G. Renzoni. "Detection of Visna Maedi virus in mesenteric lymph nodes and in other lymphoid tissues of sheep three years after respiratory infection." Veterinární Medicína 58, No. 7 (August 20, 2013): 359–63. http://dx.doi.org/10.17221/6916-vetmed.

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Visna/Maedi virus (VMV), a small ruminant lentivirus responsible for lymphoproliferative pneumonia, encephalitis, arthritis and/or mastitis in sheep, has been detected in different non-lymphoid organs. However, only a few investigations have been carried out in lymphoid tissues. In this study, some lymphoid tissues and lymph node draining or non-draining VMV target organs from five sheep infected experimentally by the respiratory route three years previously were investigated. Archival samples of spleen, red bone marrow, caudal mediastinal lymph nodes, mammary lymph nodes, popliteal lymph nodes and mesenteric lymph nodes were tested by PCR for the presence of proviral DNA. Popliteal and mesenteric lymph node samples were tested also by immunohistochemical staining of the viral capsid antigen p28. The proviral DNA was detected by PCR in all the lymphoid tissue samples from the infected sheep. The viral antigen was stained in mononuclear cells in popliteal and mesenteric lymph nodes of the infected sheep. Although the lymph nodes draining the classical target organs seem to be more infected than the others, both the viral capsid antigen and the proviral DNA were present also in lymph nodes draining non-target organs, such as the mesenteric lymph nodes. These findings show the presence of VMV in different lymphoid tissues in the late stages of infection and suggest a potential role of these tissues as a site for viral reservoir and replication, even three years after infection. &nbsp;
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Gulez, Nesrin, Guzide Aksu, Afig Berdeli, Neslihan Karaca, Sema Tanrıverdi, Necil Kutukculer, and Elif Azarsiz. "X-Linked Lymphoproliferative Syndrome and Common Variable Immunodeficiency May Not Be Differentiated bySH2D1AandXIAP/BIRC4Genes Sequence Analysis." Case Reports in Medicine 2011 (2011): 1–5. http://dx.doi.org/10.1155/2011/121258.

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The X-linked lymphoproliferative syndrome (XLP) is a rare, inherited immunodeficiency characterized by recurrent episodes of hemophagocytic lymphohistiocytosis, hypogammaglobulinemia, and/or lymphomas. Recently, X-linked inhibitor of apoptosis (XIAP/BIRC4) gene defects, in families with XLP but withoutSH2D1Agene defects, has been defined. The distinction from primary immunodeficiencies with a defined genetic cause is mandatory. A six-year-old male patient was admitted with the complaints of persistent general lymphadenopathy, for two years had fever, bilateral cervical multiple microlymphadenopathy, hepatic/splenic enlargement with laboratory findings as decreased serum immunoglobulins, negative EBV VCA IgM (viral capsid antigen) and anti-EBV EA (antibody to early D antigen), positive EBV VCA IgG (viral capsid antigen) and EBV EBNA (antibody to nuclear antigen).SH2D1Agene analysis was negative.XIAP/BIRC4sequencing revealed two novel single nucleotide variants (exon 7, 1978G > A, and 1996T > A) in the 3′UTR of the gene in both patient and mother which were not disease causing. XIAP protein expression was found to be normal. The clinical and laboratory resemblance, no gene mutations, and normal XIAP protein expression led us to think that there may be another responsible gene for XLP. The patient will to be followed up as CVID until he presents new diagnostic signs or until the identification of a new gene.
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Dzutsev, Amiran, Igor Belyakov, Dmitry Isakov, David Margulies, and Jay Berzofsky. "Avidity of CD8 T-cells sharpens immunodominance. (B9)." Journal of Immunology 178, no. 1_Supplement (April 1, 2007): LB2. http://dx.doi.org/10.4049/jimmunol.178.supp.b9.

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Abstract In the course of viral infection, the immune system exploits only a fraction of the available CTL repertoire and focuses on a few of a myriad of potentially antigenic peptides. This phenomenon, known as immunodominance, depends on a number of factors, including antigen processing and transport, MHC binding, competition for antigen presenting cells, availability of the CD8 T-cell repertoire and other mechanisms that function largely by restricting the immune response. Here we elucidate a novel mechanism that increases the immunodominance of the epitope rather by enhancing the immune response. Using a peptide-specific MHC-restricted monoclonal antibody and functional assays of CTL activation, we show that T cells with high avidity for the immunodominant, H-2Dd-restricted, P18-I10 epitope expand rapidly following immunization, and this expansion in turn determines the level of the P18-I10 epitope immunodominance. This proliferation has little dependence on the number of MHC-peptide complexes. Since most self-reactive T-cells of high avidity are depleted in the thymus, the selection of immunodominant epitopes based on the expansion of high avidity T-cells in the periphery avoids the potential for autoimmunity.
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Berkun, Y., G. Zandman-Goddard, O. Barzilai, M. Boaz, Y. Sherer, B. Larida, M. Blank, J.-M. Anaya, and Y. Shoenfeld. "Infectious antibodies in systemic lupus erythematosus patients." Lupus 18, no. 13 (October 30, 2009): 1129–35. http://dx.doi.org/10.1177/0961203309345729.

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Infections can act as environmental triggers that induce or promote systemic lupus erythematosus (SLE) in genetically predisposed individuals. New technologies, developed recently, enable simultaneous assessment of multiple antibodies. Antibodies to specific infectious agents may shed light into the mechanisms of induction of SLE. The aim of this study was to investigate the prevalence of seropositivity and the titers of antibodies to bacterial, viral, and parasitic agents in SLE patients compared with non-autoimmune controls. Sera from 260 individuals (120 SLE patients and 140 controls) were tested by the BioPlex 2200 Multiplexed Immunoassay method (BioRad) for the prevalence and titers of antibodies to eight infectious agents (Epstein—Barr virus: early antigen IgG, nuclear antigen IgG, viral capsid antigen IgG and IgM, heterophile IgM; cytomegalovirus IgG and IgM; Toxoplasma gondii IgG and IgM; rubella IgG and IgM; Treponema pallidum TPr15G, TPr17G, TPr47G; herpes simplex virus type 1 and 2 IgG; hepatitis C virus and hepatitis B core antibodies. Cytomegalovirus IgM and Epstein—Barr virus early antigen IgG (but not other Epstein—Barr virus antigens) were significantly more prevalent in SLE patients than in controls. Conversely, positive titers of hepatitis B core and rubella IgG antibodies were less prevalent in the SLE patients than in controls. Other differences in titer positivity prevalence were not detected between patients and controls. The titers of the cytomegalovirus IgM, Toxoplasma IgG, Epstein—Barr virus early antigen, and viral capsid antigen IgG antibodies were significantly higher in SLE compared with controls. Our data suggest the importance of previous exposure to infectious agents in the induction and the prevention of SLE. Lupus (2009) 18, 1129—1135.
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29

Finn, Jonathan D., Daniel J. Hui, Downey Harre, Danielle Dunn, Federico Mingozzi, Shangzhen Zhou, and Katherine A. High. "Proteasome Inhibitors Decrease AAV2 Capsid-Derived Peptide Epitope Presentation On MHC Class I Following Transduction." Blood 114, no. 22 (November 20, 2009): 695. http://dx.doi.org/10.1182/blood.v114.22.695.695.

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Abstract Abstract 695 Adeno-associated viral (AAV) vectors are one of the most extensively studied and highly used vector platforms for gene therapy applications. We have recently provided evidence for AAV capsid-derived antigen presentation through MHC class I on the surface of AAV-transduced cells, supporting the hypothesis that in the first clinical trial using AAV to treat Hemophilia B, AAV capsid proteins were presented on the surface of transduced hepatocytes, resulting in clearance by antigen-specific CD8+ T cells and consequent loss of therapeutic transgene expression. Proteasome inhibitors are small molecule compounds that are able to specifically inhibit the activity of the proteasome, resulting in a buildup of ubiquitinated proteins, increased intracellular reactive oxygen species, and a general decrease in presentation of MHCI-peptide complexes. It has previously been shown that proteasome inhibitors can have a dramatic effect on AAV transduction in vitro and in vivo. Here we describe using the FDA approved proteasome inhibitor, bortezomib, to decrease capsid antigen presentation on hepatocytes in vitro, while at the same time, enhancing gene expression in vivo. Using an AAV capsid specific T cell reporter line to analyze effects of proteasome inhibitor on antigen presentation, we demonstrated capsid antigen presentation at low MOI's, as well as inhibition of antigen presentation at clinically relevant levels of bortezomib. We also demonstrate that bortezomib can enhance FIX expression from an AAV2 vector in C57Bl/6 mice, however does not appear to enhance expression of AAV8. Based on the data presented here, it appears as if future studies using proteasome inhibitors in large animal models may be warranted. A pharmacological agent that can enhance AAV transduction, decrease T-cell activation/proliferation, and decrease antigen presentation would be a promising solution to many of the obstacles to successful translation of AAV-mediated, liver-directed gene transfer to the clinic. Disclosures: No relevant conflicts of interest to declare.
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30

Bayer, Wibke, Matthias Tenbusch, Ruth Lietz, Lena Johrden, Simone Schimmer, Klaus Überla, Ulf Dittmer, and Oliver Wildner. "Vaccination with an Adenoviral Vector That Encodes and Displays a Retroviral Antigen Induces Improved Neutralizing Antibody and CD4+ T-Cell Responses and Confers Enhanced Protection." Journal of Virology 84, no. 4 (December 9, 2009): 1967–76. http://dx.doi.org/10.1128/jvi.01840-09.

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ABSTRACT We present a new type of adenoviral vector that both encodes and displays a vaccine antigen on the capsid, thus combining in itself gene-based and protein vaccination; this vector resulted in an improved vaccination outcome in the Friend virus (FV) model. For presentation of the envelope protein gp70 of Friend murine leukemia virus on the adenoviral capsid, gp70 was fused to the adenovirus capsid protein IX. When compared to vaccination with conventional FV Env- and Gag-encoding adenoviral vectors, vaccination with the adenoviral vector that encodes and displays pIX-gp70 combined with an FV Gag-encoding vector resulted in significantly improved protection against systemic FV challenge infection, with highly controlled viral loads in plasma and spleen. This improved protection correlated with improved neutralizing antibody titers and stronger CD4+ T-cell responses. Using a vector that displays gp70 without encoding it, we found that while the antigen display on the capsid alone was sufficient to induce high levels of binding antibodies, in vivo expression was necessary for the induction of neutralizing antibodies. This new type of adenovirus-based vaccine could be a valuable tool for vaccination.
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31

Del Valle, Luis, Sahnila Enam, Cesar Lara, Judith Miklossy, Kamel Khalili, and Jennifer Gordon. "Primary Central Nervous System Lymphoma Expressing the Human Neurotropic Polyomavirus, JC Virus, Genome." Journal of Virology 78, no. 7 (April 1, 2004): 3462–69. http://dx.doi.org/10.1128/jvi.78.7.3462-3469.2004.

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ABSTRACT B lymphocytes are known as a potential site for latency and reactivation of the human neurotropic polyomavirus, JC virus (JCV). In light of recent studies on the oncogenicity of JCV and the transforming ability of the JCV early protein, T antigen, we investigated the association of JCV with B-cell lymphomas of the central nervous system. Examination of 27 well-characterized clinical specimens by gene amplification and immunohistochemistry revealed the presence of DNA sequences corresponding to the JCV early genome and the late Agnoprotein in 22 samples and the JCV late genome encoding the viral capsid proteins in 8 samples. Expression of T antigen and that of Agnoprotein by immunohistochemistry were each detected in six specimens. No evidence of the production of viral capsid proteins was observed, ruling out productive infection of JCV in the tumor cells. The results from laser capture microdissection verified the presence of JCV T-antigen sequences in tumor cells with positive immunoreactivity to antibodies against the viral proteins T antigen and Agnoprotein. Due to previous reports demonstrating an association of the Epstein-Barr virus (EBV) with transformation of B lymphocytes, EBV DNA sequences and the EBV transforming protein, latent membrane protein 1 (LMP1), were analyzed in parallel. EBV LMP1 DNA sequences were detected in 16 of 23 samples, and LMP1 expression was detected in 16 samples, 5 of which exhibited positive immunoreactivity to JCV proteins. Double labeling demonstrated coexpression of JCV T antigen and EBV LMP1 in the same cells. The detection of the JCV genome in large numbers of B-cell lymphomas and its coexistence with EBV suggest a potential role for JCV in the pathogenesis of primary CNS lymphoma.
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32

Bertrand, Kimberly A., Brenda M. Birmann, Ellen T. Chang, Donna Spiegelman, Jon C. Aster, Shumin M. Zhang, and Francine Laden. "A prospective study of Epstein-Barr virus antibodies and risk of non-Hodgkin lymphoma." Blood 116, no. 18 (November 4, 2010): 3547–53. http://dx.doi.org/10.1182/blood-2010-05-282715.

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Abstract Severe immunosuppression is an established risk factor for non-Hodgkin lymphoma (NHL), but an association with subclinical immune dysfunction is unclear. We conducted a case-control study nested in the Physicians' Health Study and the Nurses' Health Study cohorts to determine whether patterns of antibody response to Epstein-Barr virus (EBV) were associated with NHL risk. We measured antibody titers against viral capsid antigen, early antigen, and Epstein-Barr nuclear antigen (EBNA-1 and EBNA-2) in blood samples collected before diagnosis from 340 cases and 662 matched controls. Using conditional logistic regression, we estimated rate ratios (RRs) and 95% confidence intervals (CIs) for elevated versus normal titers and the ratio of anti–EBNA-1 to anti–EBNA-2 titers (≤ 1.0 vs > 1.0). We found no association between EBV serostatus, elevated titers, or an EBNA-1/EBNA-2 ratio ≤ 1.0 and NHL risk overall. For chronic lymphocytic leukemia/small lymphocytic lymphoma, suggestive associations were noted for elevated anti–EBNA-2 (RR, 1.74; 95% CI, 0.99-3.05), anti–viral capsid antigen (RR, 1.58; 95% CI, 0.79-3.14), and EBNA-1/EBNA-2 ratio ≤ 1.0 (RR, 1.52; 95% CI, 0.91-2.55). There was no evidence of heterogeneity by subtype. Overall, we found no evidence that EBV antibody profile predicts NHL risk in immunocompetent persons, with the possible exception of chronic lymphocytic leukemia/small lymphocytic lymphoma.
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33

Hoque, Mainul, Ken-ichiro Ishizu, Akiko Matsumoto, Song-Iee Han, Fumio Arisaka, Makoto Takayama, Kenji Suzuki, et al. "Nuclear Transport of the Major Capsid Protein Is Essential for Adeno-Associated Virus Capsid Formation." Journal of Virology 73, no. 9 (September 1, 1999): 7912–15. http://dx.doi.org/10.1128/jvi.73.9.7912-7915.1999.

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ABSTRACT Adeno-associated virus capsids are composed of three proteins, VP1, VP2, and VP3. Although VP1 is necessary for viral infection, it is not essential for capsid formation. The other capsid proteins, VP2 and VP3, are sufficient for capsid formation, but the functional roles of each protein are still not well understood. By analyzing a series of deletion mutants of VP2, we identified a region necessary for nuclear transfer of VP2 and found that the efficiency of nuclear localization of the capsid proteins and the efficiency of virus-like particle (VLP) formation correlated well. To confirm the importance of the nuclear localization of the capsid proteins, we fused the nuclear localization signal of simian virus 40 large T antigen to VP3 protein. We show that this fusion protein could form VLP, indicating that the VP2-specific region located on the N-terminal side of the protein is not structurally required. This finding suggests that VP3 has sufficient information for VLP formation and that VP2 is necessary only for nuclear transfer of the capsid proteins.
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34

Kashima, Haskins, Francis Kuhajda, Phoebe Mounts, and Mark Loury. "Demonstration of Human Papillomavirus Capsid Antigen in Carcinoma in Situ of the Larynx." Annals of Otology, Rhinology & Laryngology 95, no. 6 (November 1986): 603–7. http://dx.doi.org/10.1177/000348948609500613.

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We have undertaken a retrospective study to investigate the role of human papillomavirus (HPV) in the development of laryngeal carcinoma in situ (CIS). Sixty paraffin-embedded tissue specimens, collected from 20 patients with a history of laryngeal CIS, were examined for the presence of HPV capsid antigen. All but four individuals were men, with an average age at diagnosis of 64 years. An immunoperoxidase technique showed that 20 specimens from 14 patients contained detectable HPV capsid antigen. An independent evaluation for histopathologic features characteristic of HPV infection identified viral changes in the 14 patients as well as an additional two. No correlation was found between clinical course, as determined by histologic severity of vocal cord lesions, and presence of HPV. These results suggest that HPV should be considered an etiologic agent in the development of laryngeal CIS.
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Lin, S. F., R. Sun, L. Heston, L. Gradoville, D. Shedd, K. Haglund, M. Rigsby, and G. Miller. "Identification, expression, and immunogenicity of Kaposi's sarcoma-associated herpesvirus-encoded small viral capsid antigen." Journal of virology 71, no. 4 (1997): 3069–76. http://dx.doi.org/10.1128/jvi.71.4.3069-3076.1997.

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36

Dong, Yangchao, Yue Liu, Wen Jiang, Thomas J. Smith, Zhikai Xu, and Michael G. Rossmann. "Antibody-induced uncoating of human rhinovirus B14." Proceedings of the National Academy of Sciences 114, no. 30 (July 10, 2017): 8017–22. http://dx.doi.org/10.1073/pnas.1707369114.

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Rhinoviruses (RVs) are the major causes of common colds in humans. They have a nonenveloped, icosahedral capsid surrounding a positive-strand RNA genome. Here we report that the antigen-binding (Fab) fragment of a neutralizing antibody (C5) can trigger genome release from RV-B14 to form emptied particles and neutralize virus infection. Using cryo-electron microscopy, structures of the C5 Fab in complex with the full and emptied particles have been determined at 2.3 Å and 3.0 Å resolution, respectively. Each of the 60 Fab molecules binds primarily to a region on viral protein 3 (VP3). Binding of the C5 Fabs to RV-B14 results in significant conformational changes around holes in the capsid through which the viral RNA might exit. These results are so far the highest resolution view of an antibody–virus complex and elucidate a mechanism whereby antibodies neutralize RVs and related viruses by inducing virus uncoating.
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Kobayashi, Shinichi, Kenji Sakae, Yasumoto Suzuki, Kuniko Shinozaki, Mineyuki Okada, Hiroaki Ishiko, Kunio Kamata, et al. "Molecular Cloning, Expression, and Antigenicity of Seto Virus Belonging to Genogroup I Norwalk-Like Viruses." Journal of Clinical Microbiology 38, no. 9 (2000): 3492–94. http://dx.doi.org/10.1128/jcm.38.9.3492-3494.2000.

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The viral capsid protein of the Seto virus (SeV), a Japanese strain of genogroup I Norwalk-like viruses (NLVs), was expressed as virus-like particles using a baculovirus expression system. An antigen detection enzyme-linked immunosorbent assay based on hyperimmune antisera to recombinant SeV was highly specific to homologous SeV-like strains but not heterologous strains in stools, allowing us type-specific detection of NLVs.
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38

Hansra, Satyender, Sujit Pujhari, and Alexander N. Zakhartchouk. "Exploration of New Sites in Adenovirus Hexon for Foreign Peptides Insertion." Open Virology Journal 9, no. 1 (May 28, 2015): 1–6. http://dx.doi.org/10.2174/1874357901509010001.

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Adenoviral vectors are now being explored as vaccine carriers to prevent infectious diseases in humans and animals. There are two strategies aimed at the expression of a vaccine antigen by adenoviral vectors. The first includes an insertion of the foreign gene expression cassette into the E1 region. The second strategy is antigen incorporation into the viral capsid proteins. To extend this methodology, we have searched for new sites at the human adenovirus serotype 5 major capsid protein hexon for a vaccine antigen insertion. To this end, we utilized sites in the hexon hypervariable region (HVR) 7, 8 and 9 to display a 15-mer peptide containing the main neutralizing epitope of porcine reproductive and respiratory syndrome virus. However, we could not rescue the viruses with the insertions of the peptide into HVR 8 and 9, consistent with the viruses being unable to tolerate insertions at these sites. In contrast, the virus with the insertion of the peptide in HVR 7 was viable - growing well in cell culture and the inserted peptide was exposed on the virion surface.
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Zhang, Hongyi, Yanwen Li, Tianqing Peng, Malen Aasa, Li Zhang, Yingzhen Yang, and Leonard C. Archard. "Localization of Enteroviral Antigen in Myocardium and Other Tissues from Patients with Heart Muscle Disease by an Improved Immunohistochemical Technique." Journal of Histochemistry & Cytochemistry 48, no. 5 (May 2000): 579–84. http://dx.doi.org/10.1177/002215540004800501.

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SUMMARY The association of enterovirus infection and heart muscle diseases has been investigated extensively by detection of viral genomic RNA using nucleic acid hybridization and the reverse transcription-polymerase chain reaction. To further understand the role of enterovirus and its persistence in these diseases, an immunohistochemical technique was optimized to investigate the expression of viral capsid proteins in situ. A monoclonal antibody (5-D8/1) against an epitope in the N-terminus of capsid protein VP1, conserved in the enterovirus genus, was employed. To enhance sensitivity, the EnVison system was used to detect antigen-antibody complex. VP1 was detected in formalin-fixed, paraffin-embedded endomyocardial biopsy or postmortem myocardial tissues and in liver, spleen, lung, kidney, and pancreas from patients with myocarditis or dilated cardiomyopathy, but not from controls. VP1 was localized in cytoplasm of myofibers, often adjacent to necrosis and infiltrate in myocarditis, and was clustered or scattered in dilated cardiomyopathy. This technique can be used for a definitive laboratory diagnosis of enterovirus-associated diseases and for studying the mechanisms of virus persistence in chronic myocardial disease.
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Jordan, Jeanne A. "Comparison of a Baculovirus-Based VP2 Enzyme Immunoassay (EIA) to an Escherichia coli-Based VP1 EIA for Detection of Human Parvovirus B19 Immunoglobulin M and Immunoglobulin G in Sera of Pregnant Women." Journal of Clinical Microbiology 38, no. 4 (2000): 1472–75. http://dx.doi.org/10.1128/jcm.38.4.1472-1475.2000.

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A split-sample study was conducted to evaluate the clinical performance of an enzyme immunoassay that detects the human parvovirus B19 virus (B19V) immunoglobulin M (IgM) or IgG in the sera of pregnant women. The initial study compared a baculovirus-expressed VP2 enzyme immunoassay (BVP2 EIA) (Biotrin International Inc., Dublin, Ireland) with the currently available and commonly used Escherichia coli-expressed VP1 enzyme immunoassay (EVP1 EIA) (MRL Diagnostics, Cypress, Calif.). There was a high degree of agreement between the two assays in the detection of IgM antibodies (283 of 307 [92.2%]) or IgG antibodies (279 of 311 [89.7%]), with the majority of discrepancies (IgM, 17 of 24 [71%]; IgG, 16 of 31 [50%]) being due to equivocal data obtained with the EVP1 EIA. Specimens with discordant BVP2 EIA and EVP1 EIA results (23 of 24 IgM and 32 of 32 IgG results) were analyzed further by baculovirus-based VP1 immunofluorescence assays (BVP1 IFAs) (Biotrin International). The BVP2 EIA and BVP1 IFA results for 20 of 23 and 28 of 32 specimens for IgM and IgG, respectively, were concordant. In contrast, the EVP1 EIA and BVP1 IFA data for only 3 of 23 and 4 of 32 specimens for IgM and IgG, respectively, were in agreement, despite the fact that the same capsid antigen was used. Both the BVP2 EIAs and BVP1 IFAs utilize a conformational viral capsid antigen, while the EVP1 EIA uses a denatured viral capsid antigen. In conclusion, the BVP2 EIAs produced far fewer equivocal results for IgM and IgG, correlating more closely to the confirmatory BVP IFAs, than did the EVP1 EIAs and proved to be more accurate for detecting B19V antibodies in the sera of pregnant women.
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Moens, Ugo, and Andrew Macdonald. "Effect of the Large and Small T-Antigens of Human Polyomaviruses on Signaling Pathways." International Journal of Molecular Sciences 20, no. 16 (August 12, 2019): 3914. http://dx.doi.org/10.3390/ijms20163914.

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Viruses are intracellular parasites that require a permissive host cell to express the viral genome and to produce new progeny virus particles. However, not all viral infections are productive and some viruses can induce carcinogenesis. Irrespective of the type of infection (productive or neoplastic), viruses hijack the host cell machinery to permit optimal viral replication or to transform the infected cell into a tumor cell. One mechanism viruses employ to reprogram the host cell is through interference with signaling pathways. Polyomaviruses are naked, double-stranded DNA viruses whose genome encodes the regulatory proteins large T-antigen and small t-antigen, and structural proteins that form the capsid. The large T-antigens and small t-antigens can interfere with several host signaling pathways. In this case, we review the interplay between the large T-antigens and small t-antigens with host signaling pathways and the biological consequences of these interactions.
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42

Goleva, Olga, and Elena Murina. "Serologic markers of Epstein-Barr virus (EBV) reactivation in the conditions of viral encephalitis in young patients (VIR7P.1063)." Journal of Immunology 192, no. 1_Supplement (May 1, 2014): 208.15. http://dx.doi.org/10.4049/jimmunol.192.supp.208.15.

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Abstract Viral encephalitis is one of the most severe disorders that is accompanied by the processes of tissue demyelization. It can be connected with both significantly causative viruses and a potential activation of latently persisting viruses of herpes group. The impact of persisting viruses on the activation of viral encephalitis is unclear. We analyzed the blood samples from 1-14 year-old patients diagnosed with acute viral encephalitis who had a history of Epstein-Barr virus (EBV) infection. Interestingly, there were low levels of IgM to early antigen (EA), nuclear antigen (NA) and capsid antigen (VCA) but high levels of IgG as determined by ELISA. Next, we used specific stripes with the immonobilized extract of EBV antigens (Euroimmun, Germany). The analysis of IgG antibodies in all blood samples demonstrated the presence of the late phase infection markers: VCA and NA. Importantly, the early antigen EA (areas: p43, p45, p93) that is induced within 3 weeks after the initial infection, was clearly present as well. These results suggest that EBV reactivation could be one of the favorable factors that accompanies the processes of tissue demyelization of central nervous system.
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Andersson, Annika, Veronika Vetter, Ludger Kreutzer, and Georg Bauer. "Avidities of IgG directed against viral capsid antigen or early antigen: Useful markers for significant epstein-barr virus serology." Journal of Medical Virology 43, no. 3 (July 1994): 238–44. http://dx.doi.org/10.1002/jmv.1890430308.

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44

Yang, Yang, Yu Yan, Jiaxin Yin, Jie Hu, Xuefei Cai, Jieli Hu, Jie Xia, Kai Wang, Ni Tang, and Luyi Huang. "Structure-Based Discovery of N-Sulfonylpiperidine-3-Carboxamides as Novel Capsid Assembly Modulators for Potent Inhibition of HBV Replication." Viruses 14, no. 2 (February 8, 2022): 348. http://dx.doi.org/10.3390/v14020348.

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As a key element during HBV replication, a nucleocapsid is considered a promising target for the treatment of chronic hepatitis B. The present study aimed to identify small molecules as novel capsid assembly modulators with antiviral activity. Structure-based virtual screening of an integrated compound library led to the identification of several types of HBV inhibitors. Among these inhibitors, N-sulfonylpiperidine-3-carboxamides (SPCs) potently reduced the amount of secreted HBV DNA. Through structure–activity relationship studies, we identified an SPC derivative, namely, C-39, which exhibited the highest antiviral activity without causing cytotoxicity. Mechanism studies showed that C-39 dose-dependently inhibited the formation of HBV capsid, synthesis of cccDNA, e antigen (HBeAg), viral pregenomic RNA (pgRNA), and HBV DNA levels, thereby restraining HBV replication. In summary, SPCs represent a new class of capsid assembly modulators. Further optimization of SPCs is expected to obtain new antiviral drugs against HBV infection.
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Esterling, Brian A., Michael H. Antoni, Mahendra Kumar, and Neil Schneiderman. "Defensiveness, trait anxiety, and Epstein-Barr viral capsid antigen antibody titers in healthy college students." Health Psychology 12, no. 2 (March 1993): 132–39. http://dx.doi.org/10.1037/0278-6133.12.2.132.

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46

Koch, William C. "A synthetic parvovirus B19 capsid protein can replace viral antigen in antibody-capture enzyme immunoassays." Journal of Virological Methods 55, no. 1 (September 1995): 67–82. http://dx.doi.org/10.1016/0166-0934(95)00046-w.

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47

Pien, Gary C., Etiena Basner-Tschakarjan, Daniel J. Hui, Ashley N. Mentlik, Jonathan D. Finn, Nicole C. Hasbrouck, Shangzhen Zhou, et al. "Capsid antigen presentation flags human hepatocytes for destruction after transduction by adeno-associated viral vectors." Journal of Clinical Investigation 119, no. 6 (June 1, 2009): 1688–95. http://dx.doi.org/10.1172/jci36891.

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48

Tan and Jiang. "Norovirus Capsid Protein-Derived Nanoparticles and Polymers as Versatile Platforms for Antigen Presentation and Vaccine Development." Pharmaceutics 11, no. 9 (September 12, 2019): 472. http://dx.doi.org/10.3390/pharmaceutics11090472.

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Major viral structural proteins interact homotypically and/or heterotypically, self-assembling into polyvalent viral capsids that usually elicit strong host immune responses. By taking advantage of such intrinsic features of norovirus capsids, two subviral nanoparticles, 60-valent S60 and 24-valent P24 nanoparticles, as well as various polymers, have been generated through bioengineering norovirus capsid shell (S) and protruding (P) domains, respectively. These nanoparticles and polymers are easily produced, highly stable, and extremely immunogenic, making them ideal vaccine candidates against noroviruses. In addition, they serve as multifunctional platforms to display foreign antigens, self-assembling into chimeric nanoparticles or polymers as vaccines against different pathogens and illnesses. Several chimeric S60 and P24 nanoparticles, as well as P domain-derived polymers, carrying different foreign antigens, have been created and demonstrated to be promising vaccine candidates against corresponding pathogens in preclinical animal studies, warranting their further development into useful vaccines.
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Koschel, Matthias, Daniela Oed, Tudevdagwa Gerelsaikhan, Reiner Thomssen, and Volker Bruss. "Hepatitis B Virus Core Gene Mutations Which Block Nucleocapsid Envelopment." Journal of Virology 74, no. 1 (January 1, 2000): 1–7. http://dx.doi.org/10.1128/jvi.74.1.1-7.2000.

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ABSTRACT Recently we generated a panel of hepatitis B virus core gene mutants carrying single insertions or deletions which allowed efficient expression of the core protein in bacteria and self-assembly of capsids. Eleven of these mutations were introduced into a eukaryotic core gene expression vector and characterized by transcomplementation of a core-negative HBV genome in cotransfected human hepatoma HuH7 cells. Surprisingly, four mutants (two insertions [EFGA downstream of A11 and LDTASALYR downstream of R39] and two deletions [Y38-R39-E40 and L42]) produced no detectable capsids. The other seven mutants supported capsid formation and pregenome packaging/viral minus- and plus-strand-DNA synthesis but to different levels. Four of these seven mutants (two insertions [GA downstream of A11 and EHCSP downstream of P50] and two deletions [S44 and A80]) allowed virion morphogenesis and secretion. The mutant carrying a deletion of A80 at the tip of the spike protruding from the capsid was hepatitis B virus core antigen negative but wild type with respect to virion formation, indicating that this site might not be crucial for capsid-surface protein interactions during morphogenesis. The other three nucleocapsid-forming mutants (one insertion [LS downstream of S141] and two deletions [T12 and P134]) were strongly blocked in virion formation. The corresponding sites are located in the part of the protein forming the body of the capsid and not in the spike. These mutations may alter sites on the particle which contact surface proteins during envelopment, or they may block the appearance of a signal for the transport or the maturation of the capsid which is linked to viral DNA synthesis and required for envelopment.
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Lim, Chun Shen, Siang Ling Goh, Leena Kariapper, Gopala Krishnan, Yat-Yuen Lim, and Ching Ching Ng. "Inclusion bodies of recombinant Epstein–Barr virus capsid antigen p18 as potential immobilized antigens in enzyme immunoassays for detection of nasopharyngeal carcinoma." Clinica Chimica Acta 448 (August 2015): 206–10. http://dx.doi.org/10.1016/j.cca.2015.07.008.

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