Article
Medicine, Research & Experimental
Macario Martinez-Castillo, Gabriela Cruz-Robledo, Araceli Hernandez-Zavala, Emilio J. Cordova
Summary: Chronic exposure to inorganic arsenic through contaminated drinking water is a health concern, and phytochemicals like curcumin are being explored for their potential in preventing cellular damage caused by arsenic. Curcumin has been found to sensitize EBV-positive cells to the cytotoxic effects of arsenic, indicating a possible interaction between them.
EXPERIMENTAL AND THERAPEUTIC MEDICINE
(2021)
Article
Multidisciplinary Sciences
Miklos Laczik, Edina Erdos, Lilla Ozgyin, Zsuzsanna Hevessy, Eva Csosz, Gergo Kallo, Tibor Nagy, Endre Barta, Szilard Poliska, Istvan Szatmari, Balint Laszlo Balint
Summary: Isogenic B-lymphoblastoid cell lines (LCLs) are widely used for studying mutations due to their genetic stability. However, we have found that these cell lines exhibit phenotypic variability accompanied by genetic variation. In this study, we provide comprehensive datasets using next generation sequencing techniques to analyze the genomic, transcriptomic, protein-DNA interaction, and proteomic changes in LCLs. These datasets are shared with the scientific community for further investigations following the FAIR principles.
Article
Immunology
Wei Xia, Honglin Chen, Yiwei Feng, Nan Shi, Zongjian Huang, Qingyuan Feng, Xu Jiang, Guangyao He, Mao Xie, Yongjin Lai, Zhi Wang, Xiang Yi, Anzhou Tang
Summary: The study demonstrates that the tree shrew is a suitable animal model for evaluating the mechanisms of EBV infection and for developing vaccines and therapeutic drugs against EBV. This is due to its close phylogenetic relationship with humans, making it a valuable tool for studying viral infections and human diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
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
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
Biology
Elliott D. SoRelle, Joanne Dai, Emmanuela N. Bonglack, Emma M. Heckenberg, Jeffrey Y. Zhou, Stephanie N. Giamberardino, Jeffrey A. Bailey, Simon G. Gregory, Cliburn Chan, Micah A. Luftig
Summary: The study characterized single-cell transcriptomic profiles of five LCLs, revealing substantial phenotypic heterogeneity within and across LCLs likely due to intrinsic variance in primary B cells and host-pathogen dynamics. Stochastic simulations demonstrate that factors such as initial primary cell heterogeneity, random sampling, time in culture, and phenotype-specific fitness differences can contribute substantially to dynamic diversity in populations of nominally clonal cells.
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.
Article
Multidisciplinary Sciences
Stephen J. Walker, Ashley L. Wagoner, Dana Leavitt, David L. Mack
Summary: This study presents a simplified approach for generating and characterizing induced pluripotent stem cells from well-characterized and banked LCLs. By transfection with Epi5 Episomal iPSC reprogramming plasmids, the iPSCs were shown to exhibit endogenous pluripotency and trilineage potential.
Article
Virology
Bingyu Yan, Chong Wang, Srishti Chakravorty, Zonghao Zhang, Simran D. Kadadi, Yuxin Zhuang, Isabella Sirit, Yonghua Hu, Minwoo Jung, Subhransu S. Sahoo, Luopin Wang, Kunming Shao, Nicole L. Anderson, Jorge L. Trujillo-Ochoa, Scott D. Briggs, Xing Liu, Matthew R. Olson, Behdad Afzali, Bo Zhao, Majid Kazemian
Summary: We investigated the lifecycle of Epstein-Barr virus (EBV) in lymphoblastoid cell lines (LCLs) using single cell RNA sequencing (scRNA-seq) data. Two distinct clusters of cells were found, showing different expression patterns of host and viral genes. These clusters also differed in the expression of EBV lytic genes. Our study revealed the importance of HIF1-alpha signaling and super-enhancers (SEs) in the regulation of EBV latency. Perturbation of MYC or IRF4 SEs induced lytic EBV gene expression, suggesting their requirement in maintaining EBV latency.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Multidisciplinary Sciences
Munetoshi Hinata, Tetsuo Ushiku
Summary: A histology-based deep learning model was constructed to efficiently screen EBV and MSI/dMMR subtypes in gastric cancers, showing high accuracy in detecting the subgroup and highlighting intraepithelial lymphocytosis as a discriminative characteristic shared by EBV and MSI/dMMR tumors. This model offers a potential economical and less time-consuming alternative for stratifying patients who respond to ICIs.
SCIENTIFIC REPORTS
(2021)
Article
Microbiology
Francesco Baccianti, Charlene Masson, Susanne Delecluse, Zhe Li, Remy Poirey, Henri-Jacques Delecluse
Summary: EBV efficiently infects and transforms B lymphocytes by activating viral gene expression and manipulating cellular pathways to limit the immune response, according to this study. The viral particle components sequentially activate proinflammatory B lymphocyte signaling pathways, leading to viral gene expression and cytokine release. However, infection also triggers the expression of ZFP36L1, a stress protein that limits the cytokine response. This study highlights the complex interactions between EBV and host cells during infection and transformation.
Article
Biochemical Research Methods
Hansaim Lim, Chung-Jung Tsai, Ozlem Keskin, Ruth Nussinov, Attila Gursoy
Summary: HMI-PRED 2.0 is a publicly available web service that predicts host-microbe protein-protein interaction using interface mimicry. It aims to be user-friendly without requiring extensive computational experience.
Article
Medicine, General & Internal
Yin Xu, Ayako Hiyoshi, Kelsi A. Smith, Fredrik Piehl, Tomas Olsson, Katja Fall, Scott Montgomery
Summary: The study suggests that having infectious mononucleosis in childhood and especially adolescence is a risk factor associated with a diagnosis of multiple sclerosis, independent of shared familial factors.
Article
Multidisciplinary Sciences
Linlin Zhang, Mengjia Liu, Meng Zhang, Junhong Ai, Jiao Tian, Ran Wang, Zhengde Xie
Summary: Infectious mononucleosis (IM) is an acute syndrome associated with primary Epstein-Barr virus (EBV) infection. The exact pathogenic mechanism of IM remains unclear and there is currently no effective treatment. B cells and NK cells play important roles in IM, while the balance between CD4+ T cells and CD8+ T cells is crucial for lifelong control of the disease. Transcriptome sequencing of different cell populations involved in IM can help understand their functions and pathogenic mechanisms.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Article
Immunology
Mariann Gyoengyoesi, Dominika Lukovic, Julia Mester-Tonczar, Katrin Zlabinger, Patrick Einzinger, Andreas Spannbauer, Victor Schweiger, Katharina Schefberger, Eslam Samaha, Jutta Bergler-Klein, Martin Riesenhuber, Christian Nitsche, Christian Hengstenberg, Patrick Mucher, Helmuth Haslacher, Monika Breuer, Robert Strassl, Elisabeth Puchhammer-Stoeckl, Christian Loewe, Dietrich Beitzke, Ena Hasimbegovic, Thomas A. Zelniker
Summary: This study evaluated the reactivation of parvovirus-B19 and Herpesviridae family members in patients with long-COVID syndrome and found that vaccination with monovalent COVID-19 vaccines was associated with reduced fatigue and multiorgan symptoms. It also led to lower levels of DNA virus-related IgM, plasma IgG subfractions, cytomegalovirus IgG and IgM, and EBV IgM titers.
Editorial Material
Virology
Bingyu Yan, Srishti Chakravorty, Carmen Mirabelli, Luopin Wang, Jorge L. Trujillo-Ochoa, Daniel Chauss, Dhaneshwar Kumar, Michail S. Lionakis, Matthew R. Olson, Christiane E. Wobus, Behdad Afzali, Majid Kazemian
JOURNAL OF VIROLOGY
(2022)
Article
Immunology
Daniel Chauss, Tilo Freiwald, Reuben McGregor, Bingyu Yan, Luopin Wang, Estefania Nova-Lamperti, Dhaneshwar Kumar, Zonghao Zhang, Heather Teague, Erin E. West, Kevin M. Vannella, Marcos J. Ramos-Benitez, Jack Bibby, Audrey Kelly, Amna Malik, Alexandra F. Freeman, Daniella M. Schwartz, Didier Portilla, Daniel S. Chertow, Susan John, Paul Lavender, Claudia Kemper, Giovanna Lombardi, Nehal N. Mehta, Nichola Cooper, Michail S. Lionakis, Arian Laurence, Majid Kazemian, Behdad Afzali
Summary: Research suggests that Vitamin D plays a crucial role in regulating the transcriptional response of T cells, leading to the transition from pro-inflammatory to suppressive cells. In patients with severe COVID-19, disruptions in Vitamin D signaling may be responsible for dysregulation of the immune system, resulting in increased inflammation.
Article
Immunology
D. Alejandro Canaria, Maia G. Clare, Bingyu Yan, Charlotte B. Campbell, Zachariah A. Ismaio, Nicole L. Anderson, Sungtae Park, Alexander L. Dent, Majid Kazemian, Matthew R. Olson
Summary: This study reveals the importance of IL-2 in the differentiation of Th9 cells, as IL-2 signaling is required for optimal NF-kB activation and IL-9 production. The addition of the NF-kB-activating cytokine IL-1 beta can rescue Th9 differentiation under IL-2 limiting conditions by enhancing the sensitivity of Th9 cells to limited IL-2 resources.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Dhaneshwar Kumar, Subhransu Sekhar Sahoo, Daniel Chauss, Majid Kazemian, Behdad Afzali
Summary: Immune cell function relies on precise control of transcriptional output from the genome, which is regulated by environmental signals and various elements. Non-coding RNAs, although historically understudied, have been found to play crucial roles in immune cell regulation and immune-mediated diseases. Recent advances in technology and research have enabled the identification and study of ncRNAs, holding promise for future therapeutic targeting and understanding of autoimmunity.
JOURNAL OF AUTOIMMUNITY
(2023)
Article
Virology
Bingyu Yan, Chong Wang, Srishti Chakravorty, Zonghao Zhang, Simran D. Kadadi, Yuxin Zhuang, Isabella Sirit, Yonghua Hu, Minwoo Jung, Subhransu S. Sahoo, Luopin Wang, Kunming Shao, Nicole L. Anderson, Jorge L. Trujillo-Ochoa, Scott D. Briggs, Xing Liu, Matthew R. Olson, Behdad Afzali, Bo Zhao, Majid Kazemian
Summary: We investigated the lifecycle of Epstein-Barr virus (EBV) in lymphoblastoid cell lines (LCLs) using single cell RNA sequencing (scRNA-seq) data. Two distinct clusters of cells were found, showing different expression patterns of host and viral genes. These clusters also differed in the expression of EBV lytic genes. Our study revealed the importance of HIF1-alpha signaling and super-enhancers (SEs) in the regulation of EBV latency. Perturbation of MYC or IRF4 SEs induced lytic EBV gene expression, suggesting their requirement in maintaining EBV latency.
JOURNAL OF MEDICAL VIROLOGY
(2023)
Article
Immunology
Alejandro V. Villarino, Arian D. J. Laurence, Fred P. Davisi, Luis Nivelo, Stephen R. Brooks, Hong-Wei Sun, Kan Jiang, Behdad Afzali, Daniela Frasca, Lothar Hennighausen, Yuka Kanno, John J. O'Shea
Summary: This study reveals that STAT5 is a crucial regulator of energy and amino acid metabolism in CD4+ T helper cells, and it plays a role in transcriptional regulation of key enzymes and transporters. Additionally, STAT5 interacts with the mTOR signaling pathway and MYC transcription factor to regulate T-cell metabolism.
SCIENCE IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Jigar Desai, Dhaneshwar Kumar, Tilo Freiwald, Daniel Chauss, Melissa D. Johnson, Michael S. Abers, Julie M. Steinbrink, John R. Perfect, Barbara Alexander, Vasiliki Matzaraki, Brendan D. Snarr, Marissa A. Zarakas, Vasileios Oikonomou, Lakmali M. Silva, Raju Shivarathri, Emily Beltran, Luciana Negro Demontel, Luopin Wang, Jean K. Lim, Dylan Launder, Heather R. Conti, Muthulekha Swamydas, Micah T. McClain, Niki M. Moutsopoulos, Majid Kazemian, Mihai G. Netea, Vinod Kumar, Jorg Kohl, Claudia Kemper, Behdad Afzali, Michail S. Lionakis
Summary: Systemic candidiasis, a common and high-mortality nosocomial fungal infection, can be a complication of anti-complement C5-targeted monoclonal antibody treatment, which highlights the important role of C5 in antifungal immunity. Transcription of complement system genes was found to be the top biological pathway induced in candidemic patients and predictive of candidemia. Mechanistically, C5a-C5aR1 promotes fungal clearance and host survival in a mouse model of systemic candidiasis by enhancing phagocyte effector function and ensuring survival in infected tissues. Local production of C5 by phagocytes provides a crucial substrate for antifungal protection.
Article
Immunology
Rosanne Spolski, Peng Li, Vivek Chandra, Boyoung Shin, Shubham Goel, Keiko Sakamoto, Chengyu Liu, Jangsuk Oh, Min Ren, Yutaka Enomoto, Erin E. West, Stephen M. Christensen, Edwin C. K. Wan, Meili Ge, Jian-Xin Lin, Bingyu Yan, Majid Kazemian, Zu-Xi Yu, Keisuke Nagao, Pandurangan Vijayanand, Ellen V. Rothenberg, Warren J. Leonard
Summary: The IL-2 receptor alpha chain is regulated by distinct super-enhancer elements, which control constitutive and inducible expression in a cell type-specific manner. Deletion of these elements leads to autoimmune diseases and altered CD25 expression, providing new insights into cell type-specific regulation of CD25.
SCIENCE IMMUNOLOGY
(2023)
Review
Immunology
Jorge L. Trujillo-Ochoa, Majid Kazemian, Behdad Afzali
Summary: Regulatory T cells (T-reg cells) are regulated by multiple transcription factors, including FOXP3, which control their differentiation and function. The heterogeneity of T-reg cells arises from the expression of different transcription factors that fine-tune their properties. Understanding the imprinting of T-reg cell identity and function is crucial for understanding autoimmunity and developing new drugs.
NATURE REVIEWS IMMUNOLOGY
(2023)
Article
Physiology
Ranjit K. Sahu, Sandhya Xavier, Daniel Chauss, Luopin Wang, Claude Chew, Ronald Taylor, William B. Stallcup, Jennie Z. Ma, Majid Kazemian, Behdad Afzali, Jorg Kohl, Didier Portilla
Summary: This study demonstrates the pathogenic role of increased expression of the complement receptor on macrophages using novel floxed green fluorescent protein C5a receptor 1 mice and the model of folic acid-induced kidney fibrosis.
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Tilo Freiwald, Bingyu Yan, Daniel Chauss, Luopin Wang, Erin West, Carmen Mirabelli, Charles J. Zhang, Eva-Maria Nichols, Richard Gregory, Marcus Bantscheff, Sonja Ghidellidisse, Martin Kolev, Tristan Frum, Jason R. Spence, Jonathan Z. Sexton, Konstantinos D. Alysandratos, Darrell N. Kotton, Matthew R. Olson, Shahram Kordasti, Didier Portilla, Christiane Wobus, Arian Laurence, Michail S. Lionakis, Ben Afzali, Claudia Kemper, Majid Kazemian
MOLECULAR IMMUNOLOGY
(2022)
Article
Immunology
Behdad Afzali, Marina Noris, Bart N. Lambrecht, Claudia Kemper
Summary: Hyperactivation of the complement system is implicated in the pathology of COVID-19, with potential therapeutic benefits through complement inhibition. Latest research progress suggests targeting complement components for treatment may be beneficial in mitigating excessive inflammation and thrombosis in severe COVID-19 cases.
NATURE REVIEWS IMMUNOLOGY
(2022)