Article
Pharmacology & Pharmacy
Peter Garcia, Abigail Harrod, Shruti Jha, Jessica Jenkins, Alex Barnhill, Holden Lee, Merritt Thompson, Jordan Pringle Williams, James Barefield, Ashton Mckinnon, Persia Suarez, Ananya Shah, Angela J. Lowrey, Gretchen L. Bentz
Summary: Studies have shown that ML-792 inhibits SUMOylation processes in EBV-positive cell lines, while also reducing LMP1-mediated dysregulation of cellular SUMOylation, suggesting the potential of ML-792 in treating EBV-related diseases.
ANTIVIRAL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Satoru Kondo, Atsushi Okabe, Takuya Nakagawa, Keisuke Matsusaka, Masaki Fukuyo, Bahityar Rahmutulla, Hirotomo Dochi, Harue Mizokami, Yuki Kitagawa, Tomoya Kurokawa, Masato Mima, Kazuhira Endo, Hisashi Sugimoto, Naohiro Wakisaka, Kiyoshi Misawa, Tomokazu Yoshizaki, Atsushi Kaneda
Summary: Nasopharyngeal carcinoma is a malignancy associated with Epstein-Barr virus and epigenetic abnormalities play important roles in its development. The latent membrane protein 1 (LMP1) is a key factor in inducing aberrant DNA methylation of tumour suppressor genes. This study identified LMP1-inducible methylation genes and demonstrated that DERL3 repression by DNA methylation contributes to the progression of nasopharyngeal carcinoma. The findings suggest potential targets for therapeutic intervention.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Review
Oncology
Angela Kwok-Fung Lo, Christopher W. Dawson, Hong Lok Lung, Ka-Leung Wong, Lawrence S. Young
Summary: LMP1, as a critical protein in EBV infection, plays an important role in the development of NPC by activating multiple pathways. Targeting LMP1 protein for treatments may be a novel therapeutic strategy for EBV-driven malignancies.
FRONTIERS IN ONCOLOGY
(2021)
Review
Medicine, Research & Experimental
Prankur Awasthi, Manish Dwivedi, Dhruv Kumar, Saba Hasan
Summary: Epstein-Barr Virus (EBV) infection is associated with various lymphomas, carcinomas, and disorders. The carcinogenic potential of EBV is related to latent membrane protein 1 (LMP1), which plays an essential role in the transformation of fibroblasts and primary lymphocytes. LMP1, a constitutively active transmembrane protein of the tumour necrosis factor receptor (TNFR) superfamily, interferes with and influences numerous host cellular activities and functions, contributing to the pathogenesis of EBV-associated malignancies.
Review
Biochemistry & Molecular Biology
Fedor Berditchevski, Eanna Fennell, Paul G. Murray
Summary: Induced waves of calcium fluxes play a crucial role in the differentiation and maturation of B-cells, while dysregulation of calcium fluxes may lead to B-cell lymphomagenesis. Several cytotoxic drugs target calcium-dependent pathways for lymphoma treatment.
Article
Chemistry, Analytical
Han-Yun Hsieh, Jia-Xian Luo, Yi-Hong Shen, Shu-Cheng Lo, Yi-Chiung Hsu, Hidetoshi Tahara, Yu-Jui Fan, Pei-Kuen Wei, Horn-Jiunn Sheen
Summary: This study developed a rapid and highly sensitive EBV screening method using a nanofluidic preconcentrator integrated with a nanoslit Fano resonance biosensor to detect latent membrane protein 1 (LMP1) for EBV diagnosis. Through nanoimprinting and aluminum deposition, a low-cost nanoslit plasmonic sensing chip was mass-produced, achieving a limit of detection of 100 pg/ml and a sensing range of 100 pg/ml to 10 μg/ml.
SENSORS AND ACTUATORS B-CHEMICAL
(2022)
Article
Microbiology
Jun Li, Yan Zhang, Lingling Sun, Song Liu, Menghe Zhao, Bing Luo
Summary: This study found that EBV induces the overexpression of p53 protein in EBVaGC and NPC cells through the H19/miR-675-5p axis, leading to cell proliferation and apoptosis inhibition.
MICROBIOLOGY SPECTRUM
(2022)
Article
Immunology
Omkar Indari, Annu Rani, Budhadev Baral, Suleyman Ergun, Kiran Bala, Srikanth Karnati, Hem Chandra Jha
Summary: Viruses exploit peroxisomal compartment for successful infection. This study investigates the modulation of peroxisomal proteins in EBV transformed cell lines and during acute EBV infection. The results reveal distinct regulation of peroxisomal proteins in EBV infected cells and highlight the importance of investigating the manipulation of the peroxisomal compartment in EBV pathologies.
MICROBIAL PATHOGENESIS
(2023)
Article
Multidisciplinary Sciences
Yoshimi Enose-Akahata, Limin Wang, Fahad Almsned, Kory R. Johnson, Yair Mina, Joan Ohayon, Xin Wei Wang, Steven Jacobson
Summary: Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS), and the cause of MS remains unknown. This study investigated the antibody responses against various viruses in the cerebrospinal fluid (CSF) and serum of MS patients, and found significant differences compared to healthy volunteers, as well as a pattern of antibody responses against multiple viruses, including Epstein-Barr virus. These findings indicate that virus-specific antibody signatures might reflect the disease-associated inflammatory milieu in the CSF of patients with neuroinflammatory diseases.
Article
Oncology
Fenggang Yu, Nicholas L. Syn, Yanan Lu, Qing Yun Chong, Junyun Lai, Wei Jian Tan, Boon Cher Goh, Paul A. MacAry, Lingzhi Wang, Kwok Seng Loh
Summary: The Asia Pacific EBV strain Yu103 exhibits a unique capacity to infect and transform both B-lymphocytes and nasopharyngeal epithelial cells, lying midway along the spectrum of EBV strains known to drive lymphomagenesis or carcinogenesis. This EBV isolate is currently the only one shown to drive human nasopharyngeal carcinoma and B-lymphoma, making it a powerful novel platform for research on EBV-driven hematological and epithelial malignancies.
FRONTIERS IN ONCOLOGY
(2021)
Article
Chemistry, Physical
Mengran Guo, Xing Duan, Xingchen Peng, Zhaohui Jin, Hai Huang, Wen Xiao, Qian Zheng, Yongqi Deng, Na Fan, Kepan Chen, Xiangrong Song
Summary: In this study, a lipid-based LMP2-mRNA vaccine was developed and shown to effectively express LMP2 and stimulate antigen-specific T-cell responses in cell assays. It significantly inhibited tumor growth in an LMP2-expressing tumor model after three doses of vaccination.
Article
Pathology
Sudipta Samanta, Muthukaruppan Swaminathan, Jianing Hu, Khai Tuck Lee, Ajitha Sundaresan, Chuan Keng Goh, Chor Hiang Siow, Kwok Seng Loh, Soh Ha Chan, Joshua K. Tay, Ian Cheong
Summary: The use of immunofluorescence assay for detecting serum Epstein-Barr virus antibodies is the gold standard screening test for nasopharyngeal cancer in high-risk populations. This study demonstrates that integrating deep learning with automated fuzzy inference can improve the scalability and accuracy of NPC detection.
AMERICAN JOURNAL OF PATHOLOGY
(2022)
Article
Oncology
Hui-Chen Lin, Yao Chang, Ruo-Yu Chen, Liang-Yi Hung, Paul Chih-Hsueh Chen, Ya-Ping Chen, L. Jeffrey Medeiros, Po-Min Chiang, Kung-Chao Chang
Summary: The study found that EBV-LMP1 enhances autophagy and promotes the viability of HL cells, suggesting that autophagic inhibition may be a potential therapeutic strategy for treating patients with HL, especially EBV-positive cases.
Review
Biochemistry & Molecular Biology
Gadde Shareena, Dileep Kumar
Summary: Epstein Barr virus (EBV) is the first oncogenic virus in humans and is closely associated with various lymphoproliferative and malignant diseases. EBV has a biphasic viral life cycle, consisting of a latent period and lytic replication, with B-cells playing a critical role in latent gene expression and immune recognition evasion. Dysregulation of epigenetic regulation, particularly DNA methylation, in both viral and host genome expression, is closely related to carcinogenesis and long-lasting phenotypes in malignancies.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
(2023)
Article
Hematology
Hannes Vietzen, Philippe L. Furlano, Jan J. Cornelissen, Georg A. Boehmig, Peter Jaksch, Elisabeth Puchhammer-Stoeckl
Summary: This study found that nonclassic human leukocyte antigen E (HLA-E)-restricted immune responses have a significant impact on the development of Epstein-Barr virus (EBV) diseases in the individual host. The highly expressed HLA-E*0103/0103 genotype is protective against infectious mononucleosis (IM) by inducing potent EBV BZLF1-specific HLA-E-restricted CD8(+) T-cell responses. Variations in the inhibitory NKG2A/LMP-1/HLA-E axis are associated with the risk of symptomatic EBV reactivations in both immunocompetent individuals and immunocompromised transplant recipients.
Review
Biochemistry & Molecular Biology
Amit Bar-Or, Michael P. Pender, Rajiv Khanna, Lawrence Steinman, Hans-Peter Hartung, Tap Maniar, Ed Croze, Blake T. Aftab, Gavin Giovannoni, Manher J. Joshi
TRENDS IN MOLECULAR MEDICINE
(2020)
Review
Biochemistry & Molecular Biology
Debottam Sinha, Corey Smith, Rajiv Khanna
Summary: Tumor-intrinsic factors play a crucial role in resistance to adoptive T cell therapy (ACT), highlighting the potential of repurposing molecular targeted therapies to overcome intratumoral resistance. Combining targeted therapy and ACT is proposed as a new paradigm to enhance the clinical efficacy of cancer therapeutics.
TRENDS IN MOLECULAR MEDICINE
(2021)
Editorial Material
Hematology
Debottam Sinha, Rajiv Khanna
Summary: This study introduces a novel multicolor flow cytometry technology to uncover the crucial role of myeloid-derived suppressor cells in EBV-associated lymphoproliferative diseases, with a focus on the proliferation of EBV-positive natural killer (NK) cells and T cells.
Article
Immunology
Mohammed Altaf, Katie E. Lineburg, Pauline Crooks, Sweera Rehan, Katherine K. Matthews, Michelle A. Neller, George R. Ambalathingal, Debottam Sinha, Michelle Grant, Peter M. A. Hopkins, Daniel Chambers, Rajiv Khanna, Corey Smith
Summary: In lung transplant recipients, pretransplant CMV-NIR status is significantly associated with a higher incidence of CMV reactivation posttransplant. Therefore, dysfunctional CMV immunity increases the risk of viral reactivation after transplantation.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Article
Virology
Eunok Lee, Kerrie Sandgren, Gabriel Duette, Vicki V. Stylianou, Rajiv Khanna, John-Sebastian Eden, Emily Blyth, David Gottlieb, Anthony L. Cunningham, Sarah Palmer
Summary: Developing optimal T-cell response assays for SARS-CoV-2 is crucial for measuring immunity duration and vaccine efficacy. By using immunoinformatics analysis, we identified 57 immunogenic peptides with potential global cellular immune response coverage. 18 of these peptides have limited homology to seasonal human coronaviruses, making them promising candidates for specific T-cell immunity tests for SARS-CoV-2. Two peptides elicited effector responses in CD8+ T cells from SARS-CoV-2 convalescent patients.
JOURNAL OF VIROLOGY
(2021)
Correction
Biochemistry & Molecular Biology
Amit Bar-Or, Michael P. Pender, Rajiv Khanna, Lawrence Steinman, Hans-Peter Hartung, Tap Maniar, Ed Croze, Blake T. Aftab, Gavin Giovannoni, Manher A. Joshi
TRENDS IN MOLECULAR MEDICINE
(2021)
Article
Oncology
Debottam Sinha, Sriganesh Srihari, Kirrliee Beckett, Laetitia Le Texier, Matthew Solomon, Archana Panikkar, George R. Ambalathingal, Lea Lekieffre, Pauline Crooks, Sweera Rehan, Michelle A. Neller, Corey Smith, Rajiv Khanna
Summary: Studies have shown that overcoming resistance to in vivo T-cell therapy can be achieved through the sequential infusion of two different allogeneic T-cell therapies restricted by different HLA alleles targeting EBV. Furthermore, the combination of inhibition of the programmed cell death protein-1/programmed death-ligand 1 axis with EBV-specific T-cell therapy significantly improves overall survival in tumor-bearing mice.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Immunology
Katie E. Lineburg, Emma J. Grant, Srividhya Swaminathan, Demetra S. M. Chatzileontiadou, Christopher Szeto, Hannah Sloane, Archana Panikkar, Jyothy Raju, Pauline Crooks, Sweera Rehan, Andrea T. Nguyen, Lea Lekieffre, Michelle A. Neller, Zhen Wei Marcus Tong, Dhilshan Jayasinghe, Keng Yih Chew, Christian A. Lobos, Hanim Halim, Jacqueline M. Burrows, Alan Riboldi-Tunnicliffe, Weisan Chen, Lloyd D'Orsogna, Rajiv Khanna, Kirsty R. Short, Corey Smith, Stephanie Gras
Summary: Efforts are being made to understand the immune response to SARS-CoV-2, with a focus on T cell immunity and cross-recognition with seasonal coronaviruses. Research has shown that the N protein of SARS-CoV-2 induces an immunodominant response and T cells demonstrate cross-reactivity towards certain coronaviruses through specific peptide conformations.
Article
Oncology
Corey Smith, Margaret McGrath, Michelle A. Neller, Katherine K. Matthews, Pauline Crooks, Laetitia Le Texier, Benedict Panizza, Sandro Porceddu, Rajiv Khanna
Summary: This study presented a novel case report of a patient with metastatic nasopharyngeal carcinoma who was successfully treated with a combination of EBV-specific ACT and PD-1 blockade therapy, resulting in complete resolution of metastatic disease for 22 months. Follow-up immunological analysis showed significant restructuring of the global T-cell repertoire coincident with the clinical response, providing an important platform for further translating these findings to a larger cohort of NPC patients.
NPJ PRECISION ONCOLOGY
(2021)
Article
Peripheral Vascular Disease
Ngar Woon Kam, Ka Chun Wu, Wei Dai, Ying Wang, Leo Yik Chun Yan, Reshma Shakya, Rajiv Khanna, Yanru Qin, Simon Law, Anthony Wing Ip Lo, Victor Ho Fun Lee, Xin-Yuan Guan, Dora Lai-Wan Kwong
Summary: Different functions and profiles of B-cell subsets in various cancers have been reported. In esophageal squamous cell carcinoma (ESCC), proliferating B cells are predominantly found in the peritumoral region with high expression of HMGB1. Cancer-derived HMGB1 modulates B cells to promote angiogenesis in ESCC microenvironment.
Article
Microbiology
Vijayendra Dasari, Kirrilee Beckett, Shane Horsefield, George Ambalathingal, Rajiv Khanna
Summary: Researchers have designed a novel bivalent subunit vaccine against CMV, which combines CMV-encoded oligomeric glycoprotein B, polyepitope protein, and a TLR9 agonist to induce both humoral and cellular immune responses. The vaccine generated durable anti-viral antibodies and CMV-specific T cell responses in mice, and showed the potential to prevent CMV-associated complications.
Article
Immunology
Katie E. Lineburg, Michelle A. Neller, George R. Ambalathingal, Laetitia Le Texier, Jyothy Raju, Srividhya Swaminathan, Lea Lekieffre, Caitlyn Smith, Sweera Rehan, Pauline Crooks, Archana Panikkar, Sriganesh Srihari, Rajiv Khanna, Corey Smith
Summary: This study demonstrates that most recipients of the ChAdOx1-S vaccine generated a T helper 1 response (IFN-gamma and/or IL-2) following the first dose of the vaccine, with a strong correlation between the magnitude of the IFN-gamma and IL-2 response. While some individuals showed production of other cytokines without generating IFN-gamma and IL-2, there was no correlation in magnitude, nor was there a correlation between sex or age and the magnitude of the response.
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2021)
Meeting Abstract
Cell & Tissue Engineering
P. Foubert, S. Srihari, L. Le Textier, R. R. Shen, F. Forozan, C. Smith, R. Khanna, B. T. Aftab
Meeting Abstract
Cell & Tissue Engineering
G. Ambalathingal Thomas, R. S. FRancis, D. Corvino, S. Srihari, M. Nellar, B. T. Aftab, C. Smith, R. Khanna
Article
Immunology
George R. Ambalathingal, Ross S. Francis, Dillon Corvino, Sriganesh Srihari, Blake T. Aftab, Corey Smith, Rajiv Khanna
CLINICAL & TRANSLATIONAL IMMUNOLOGY
(2020)
