Article
Biology
Michael L. Wood, Colin D. Veal, Rita Neumann, Nicolas M. Suarez, Jenna Nichols, Andrei J. Parker, Diana Martin, Simon P. R. Romaine, Veryan Codd, Nilesh J. Samani, Adriaan A. Voors, Maciej Tomaszewski, Louis Flamand, Andrew J. Davison, Nicola J. Royle
Summary: Human herpesviruses 6A and 6B can transition between telomere-integrated and free virus forms, with mainly maternal transmission of acquired virus observed in families. Some healthy adults have shown telomere integration of acqHHV-6B in saliva, indicating latency. The excision of viral genome from telomeres in iciHHV-6B carriers is high and tissue-specific, with potential reactivation from circular extrachromosomal forms.
Review
Immunology
Anthony L. Komaroff, Roberta Rizzo, Jeffrey L. Ecker
Summary: HHV-6A and HHV-6B are ancient human viruses that can cause lifelong infection and are associated with various diseases. These viruses may have an impact on infertility, preeclampsia, and other reproductive diseases, but further research is needed to fully understand their role.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Virology
Sara A. Dochnal, Alison K. Francois, Anna R. Cliffe
Summary: Human herpesviruses establish a latent infection in specialized cell types, where their genomes associate with cellular histone proteins and assemble into heterochromatin; The reversible form of heterochromatin known as facultative heterochromatin, characterized by polycomb silencing, allows gene expression and reactivation; Herpesviruses provide an optimal system to study how de novo facultative heterochromatin is targeted to DNA regions and contribute to silencing, which could inform on the mechanism of persistence and reactivation of these pathogenic human viruses.
Article
Microbiology
Misa Miyake, Yoshiki Kawamura, Naoko Ishihara, Shigetaka Suzuki, Hiroki Miura, Yoko Sakaguchi, Masaharu Tanaka, Yoshiyuki Takahashi, Seiji Kojima, Hiroshi Toyama, Jun Natsume, Tetsushi Yoshikawa
Summary: The study found that HHV-6B infection may impair the hippocampus in pediatric HSCT recipients, with a significant impact on the volume ratio of the right and left hippocampus. Some patients with HHV-6B infection developed encephalopathy at the time of infection, but others did not show neurological symptoms.
Review
Microbiology
Anthony L. Komaroff, Philip E. Pellett, Steven Jacobson
Summary: This review examines the evidence that Human herpesvirus 6A (HHV-6A) and human herpesvirus 6B (HHV-6B) may trigger neurological diseases in humans, including encephalitis in immunocompromised patients and febrile seizures in infants and children. It also discusses the criteria for linking infectious agents to neurologic diseases and evaluates the extent to which these criteria have been met for HHV-6A/B and various neurological conditions.
CLINICAL MICROBIOLOGY REVIEWS
(2021)
Article
Oncology
Aurora Taira, Kimmo Palin, Anna Kuosmanen, Niko Valimaki, Outi Kuittinen, Outi Kuismin, Eevi Kaasinen, Kristiina Rajamaki, Lauri A. Aaltonen
Summary: Recent studies have shown that vitamin C can enhance the demethylation activity of the TET2 gene and reduce DNA hypermethylation. This suggests that vitamin C may play a role in preventing hematological malignancies in individuals with TET2 dysfunction.
CLINICAL EPIGENETICS
(2023)
Article
Biochemistry & Molecular Biology
Wanhai Qin, Bruno Crestani, C. Arnold Spek, Brendon P. Scicluna, Tom van der Poll, JanWillem Duitman
Summary: This study found that TET2 expression is decreased in IPF patients and AEC2 cells, but AEC2-specific TET2 deficiency does not affect bleomycin-induced pulmonary fibrosis.
Article
Virology
Vivien R. Schack, Litten Sorensen Rossen, Clara Christina Ekebjaerg, Katrine Kyd Holstein Thuesen, Bettina Bundgaard, Per Hollsberg
Summary: The genetic approach showed that CD46 is critical for infection by HHV-6A, while CD9 modulates infection by promoting CD46-dependent infection and impairing CD46-independent infection. HHV-6B appears to be more promiscuous and may use different entry mechanisms in various cells.
JOURNAL OF VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Qi Qi, Qianqian Wang, Kailing Liu, Jiangyue Bian, Zhixuan Yu, Jian Hou
Summary: Tet dioxygenases can induce DNA demethylation and play important roles in mammalian development. Overexpression of Tet1 and Tet2 can alter the methylation landscape of zygotes and impair embryonic development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Karishma J. B. Pratt, Jeremy M. Shea, Laura Remesal-Gomez, Gregor Bieri, Lucas K. Smith, Julien Couthouis, Christopher P. Chen, Irena J. Roy, Geraldine Gontier, Saul A. Villeda
Summary: Loss of Tet2 in adult neurons enhances cognitive function, while overexpression of Tet2 impairs memory. Neuronal Tet2 regulates cognitive function by modulating hydroxymethylation of genes involved in synaptic transmission and dendritic complexity.
Article
Virology
Lindsey B. Crawford, Meaghan H. Hancock, Hillary M. Struthers, Daniel N. Streblow, Andrew D. Yurochko, Patrizia Caposio, Felicia D. Goodrum, Jay A. Nelson
Summary: This study demonstrates that CD34(+) progenitor cells derived from embryonic stem cells can serve as a model for HCMV latency, and the virus may either latently or persistently infect specific subpopulations of CD34(+) cells.
JOURNAL OF VIROLOGY
(2021)
Article
Biochemistry & Molecular Biology
Ekaterina Romanova, Anatoliy Zubritskiy, Anna Lioznova, Adewale J. Ogunleye, Vasily A. Golotin, Anna A. Guts, Andreas Lennartsson, Oleg N. Demidov, Yulia A. Medvedeva
Summary: Acute myeloid leukemia (AML) is a rapidly progressing disease with a high mortality rate. Mutations in transcription factors RUNX1 and CEBPA in AML patients can affect the methylation of regulatory sites, leading to gene silencing, most likely in a TET2-dependent manner. Demethylation therapy can restore gene expression and increase sensitivity to chemotherapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Virology
Jolien Van Cleemput, Orkide O. Koyuncu, Kathlyn Laval, Esteban A. Engel, Lynn W. Enquist
Summary: The study reveals the potential indirect role of tegument protein UL13 in promoting productive infection by phosphorylating other tegument proteins, suggesting its involvement in escape from genome silencing and initiation of productive infection in neurons.
JOURNAL OF VIROLOGY
(2021)
Article
Immunology
Elham Bahramian, Mercede Furr, Jerry T. Wu, Ruben Michael Ceballos
Summary: Within the family Herpesviridae, there are three human herpesviruses that have been described: HHV-6A, HHV-6B, and HHV-7. Despite their high genetic sequence similarity, HHV-6A and HHV-6B are now recognized as distinct viruses. The mechanisms of action and relative contributions of these viruses to neurological dysfunction are unclear. This study shows that both HHV-6A and HHV-6B can infect different nerve cell types and neurotransmitter phenotypes, and HHV-6A induces more severe cytopathic effects. These findings provide insights into potential mechanisms for HHV6-induced epileptogenesis.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Genetics & Heredity
Ye Chen, Yuyan Wang, Ping Zhou, Hao Huang, Rui Li, Zhen Zeng, Zifeng Cui, Rui Tian, Zhuang Jin, Jiashuo Liu, Zhaoyue Huang, Lifang Li, Zheying Huang, Xun Tian, Meiying Yu, Zheng Hu
Summary: This study constructed a virus integration site (VIS) Atlas database, which collected integration breakpoints for three most prevalent oncoviruses. The database provides a genome browser, a platform to discover integration patterns, and a statistics interface for a comprehensive investigation of genotype specific integration features.
GENOMICS PROTEOMICS & BIOINFORMATICS
(2023)
Article
Clinical Neurology
R. F. Radlberger, I Sakic, T. Moser, G. Pilz, A. Harrer, P. Wipfler
Summary: The study reported differences in the immune phenotype of a patient with disease activity during cladribine treatment compared to patients without disease activity, and discussed possible causes for these deviations as caveats regarding treatment sequelae. Both the case and controls showed similar reductions in memory B cells in response to cladribine, but the case exhibited accelerated repopulation dynamics of naive B cells with almost 3-fold hyperrepopulation compared to baseline levels. Additionally, the case had lower pre-treatment levels of CD4+ and CD8+ T cells and memory B cells compared to controls.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2021)
Letter
Clinical Neurology
C. O'Sullivan, F. Zach, T. Moser, G. Pilz, A. Harrer, E. Trinka, C. Enzinger, J. A. R. Pfaff, P. Wipfler
JOURNAL OF NEUROLOGY
(2022)
Review
Clinical Neurology
Natasha Smyrke, Nicky Dunn, Chantelle Murley, Deborah Mason
Summary: The study indicates that people with multiple sclerosis have a reduced overall survival and an increased risk of death, particularly from cardiovascular, respiratory and infectious diseases, accidents, and suicide. This situation does not seem to have changed over the past 65 years.
ACTA NEUROLOGICA SCANDINAVICA
(2022)
Article
Medicine, General & Internal
Ferdinand Otto, Christine Harrer, Georg Pilz, Peter Wipfler, Andrea Harrer
Summary: Cerebrospinal fluid (CSF) has seen a resurgence in diagnostics and research, but advancements in CSF cell analysis have been limited. While CSF cell count and cytology have been central in diagnosing CNS diseases, the lack of incorporation of modern immune phenotyping technologies has left valuable information unexplored. This gap is particularly concerning given the important role of CSF cells in CNS immune defense and autoimmune processes, as well as the diagnostic challenges posed by overlapping infectious and immune-mediated CNS diseases.
Article
Clinical Neurology
Tobias Moser, Ferdinand Otto, Ciara O'Sullivan, Wolfgang Hitzl, Georg Pilz, Andrea Harrer, Eugen Trinka, Peter Wipfler
Summary: Despite concomitant anti-CD20 therapy, people with multiple sclerosis (pwMS) still exhibit humoral response to recall antigens from COVID-19 booster vaccines. This finding could have implications in the management of individuals about to start B cell medications.
MULTIPLE SCLEROSIS AND RELATED DISORDERS
(2022)
Article
Clinical Neurology
Gabriel Bsteh, Christiane Gradl, Bettina Heschl, Harald Hegen, Franziska Di Pauli, Hamid Assar, Fritz Leutmezer, Gerhard Traxler, Nik Krajnc, Gudrun Zulehner, Maria-Sophia Hiller, Paulus Rommer, Peter Wipfler, Michael Guger, Christian Enzinger, Thomas Berger
Summary: This study analyzed predictors of COVID-19 outcomes in individuals with multiple sclerosis, finding that the severity of the course primarily depends on a priori risk factors. Vaccination significantly reduces the risk of severe COVID-19 in individuals with multiple sclerosis.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Gabriel Bsteh, Hamid Assar, Christiane Gradl, Bettina Heschl, Maria-Sophie Hiller, Nik Krajnc, Franziska Di Pauli, Harald Hegen, Gerhard Traxler, Fritz Leutmezer, Peter Wipfler, Gudrun Zulehner, Michael Guger, Christian Enzinger, Thomas Berger
Summary: The long-term outcome of COVID-19 in pwMS is favorable, with the majority of patients experiencing complete recovery and only a small proportion suffering from persistent symptoms. COVID-19 does not increase the risk of relapse or disability in pwMS.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Multidisciplinary Sciences
Joe N. Frost, Sarah K. Wideman, Alexandra E. Preston, Megan R. Teh, Zhichao Ai, Lihui Wang, Amy Cross, Natasha White, Yavuz Yazicioglu, Michael Bonadonna, Alexander J. Clarke, Andrew E. Armitage, Bruno Galy, Irina A. Udalova, Hal Drakesmith
Summary: Low plasma iron induced by hepcidin inhibits neutrophil production and alters their effector functions, while having no significant effect on other types of white blood cells. Antagonizing endogenous hepcidin can enhance neutrophil production during acute inflammation. These findings suggest that plasma iron plays a role in modulating the profile of innate immunity, with potential therapeutic implications.
Article
Biochemistry & Molecular Biology
Felix Clemens Richter, Matthias Friedrich, Nadja Kampschulte, Klara Piletic, Ghada Alsaleh, Ramona Zummach, Julia Hecker, Mathilde Pohin, Nicholas Ilott, Irina Guschina, Sarah Karin Wideman, Errin Johnson, Mariana Borsa, Paula Hahn, Christophe Morriseau, Bruce D. Hammock, Henk Simon Schipper, Claire M. Edwards, Rudolf Zechner, Britta Siegmund, Carl Weidinger, Nils Helge Schebb, Fiona Powrie, Anna Katharina Simon
Summary: Lipids play a major role in inflammatory diseases through altering inflammatory cell functions. Autophagy, a lysosomal degradation pathway, is found to regulate lipid availability, which affects inflammation. Loss of autophagy gene Atg7 in adipocytes exacerbates intestinal inflammation by causing an imbalance of oxylipins, reducing IL-10 secretion, and exacerbating intestinal inflammation through the cytochrome P450-EPHX pathway.
Article
Biochemistry & Molecular Biology
Fabian Foettinger, Georg Pilz, Peter Wipfler, Andrea Harrer, Jan Marco Kern, Eugen Trinka, Tobias Moser
Summary: Therapeutic plasma exchange (TPE) is used for drug-resistant neuroimmunological disorders, but its mechanism of action remains poorly understood. This study investigated changes in immune components associated with TPE and found that pathogen-specific antibody levels were reduced post-TPE and recovered during follow-ups. Ig subclasses were also reduced post-TPE and showed subsequent recovery. IL-6 and CRP concentrations increased post-TPE, while no alterations were found in B- and T-cell populations.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Michael Seiberl, Julia Feige, Patrick Hilpold, Wolfgang Hitzl, Lukas Machegger, Arabella Buchmann, Michael Khalil, Eugen Trinka, Andrea Harrer, Peter Wipfler, Tobias Moser
Summary: This study investigated the impact of cladribine on serum neurofilament light chain (sNfL) and its potential as a predictor of long-term treatment response. The results showed that cladribine significantly reduced sNfL levels, but baseline and 12-month sNfL assessments failed to predict clinical and radiological treatment response.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Clinical Neurology
Tobias Moser, Ciara O'Sullivan, Ferdinand Otto, Wolfgang Hitzl, Georg Pilz, Kerstin Schwenker, Cornelia Mrazek, Elisabeth Haschke-Becher, Eugen Trinka, Peter Wipfler, Andrea Harrer
Summary: The inhibition of humoral responses to COVID-19 vaccines induced by anti-CD20 therapy is transient, and antibody production is more pronounced after discontinuation of anti-CD20 treatment for 18 months. The immunological effect on B-cell counts appears to wane by the same time.
THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS
(2022)
Article
Clinical Neurology
Julia Feige, Klaus Berek, Michael Seiberl, Patrick Hilpold, Wolfgang Hitzl, Franziska Di Pauli, Harald Hegen, Florian Deisenhammer, Eugen Trinka, Andrea Harrer, Peter Wipfler, Tobias Moser
Summary: Anti-CD20 therapies decrease humoral response to SARS-CoV-2 immunization. Peripheral B cells are required to generate antibodies to neo-antigens but not for a recall response during anti-CD20 therapy.
NEUROLOGY INTERNATIONAL
(2022)
Article
Biochemistry & Molecular Biology
Eirini Mylonaki, Michael Seiberl, Neil Jones, Heike Bernhard, Ferdinand Otto, Georg Pilz, Eugen Trinka, Peter Wipfler
Summary: Tick-borne encephalitis is a common viral disease transmitted by ticks in Middle-East Europe and North Asia. This case report from Austria highlights the importance of considering tick-borne encephalitis in the differential diagnosis of febrile diseases and the potential transmission through unpasteurized dairy products.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Joe N. Frost, Tiong Kit Tan, Munawar Abbas, Sarah K. Wideman, Michael Bonadonna, Nicole U. Stoffel, Katherine Wray, Barbara Kronsteiner, Gaby Smits, Dean R. Campagna, Tiago L. Duarte, Jose M. Lopes, Akshay Shah, Andrew E. Armitage, Joao Arezes, Pei Jin Lim, Alexandra E. Preston, David Ahern, Megan Teh, Caitlin Naylor, Mariolina Salio, Uzi Gileadi, Simon C. Andrews, Susanna J. Dunachie, Michael B. Zimmermann, Fiona R. M. van der Klis, Vincenzo Cerundolo, Oliver Bannard, Simon J. Draper, Alain R. M. Townsend, Bruno Galy, Mark D. Fleming, Marie C. Lewis, Hal Drakesmith
Summary: The study found that hypoferremia severely impairs immune responses to vaccinations, but providing extra iron can improve this situation. Experiments on mice and piglets revealed that iron deficiency weakens immunity to vaccines and pathogens.