Article
Immunology
Alanna G. Spiteri, Rachel L. Terry, Claire L. Wishart, Thomas M. Ashhurst, Iain L. Campbell, Markus J. Hofer, Nicholas J. C. King
Summary: A novel gating strategy was developed to distinguish microglia and infiltrating myeloid cells during West Nile virus infection, revealing significant phenotypic changes in the cells. Four distinct microglia subsets were identified, with two additional populations of macrophages recruited from the bone marrow during infection. Detailed kinetic analysis showed alterations in microglia subsets and their phenotypes in response to infection, providing valuable insights for potential therapeutic approaches targeting these cells.
JOURNAL OF NEUROINFLAMMATION
(2021)
Review
Clinical Neurology
Alanna G. Spiteri, Claire L. Wishart, Roger Pamphlett, Giuseppe Locatelli, Nicholas J. C. King
Summary: Microglia and monocytes play crucial roles in neurological diseases, but the lack of discriminating markers and experimental systems has historically hindered the precise definition of their roles. Recent advancements in single-cell technologies, new markers, and drugs have improved the ability to distinguish these cell types, yet limitations in focusing on specific cell types, diseases or experimental approaches have restricted the broader connections between phenotype and function.
ACTA NEUROPATHOLOGICA
(2022)
Review
Immunology
Andres Vidal-Itriago, Rowan A. W. Radford, Jason A. A. Aramideh, Cindy Maurel, Natalie M. M. Scherer, Emily K. K. Don, Albert Lee, Roger S. S. Chung, Manuel B. B. Graeber, Marco Morsch
Summary: Microglia, originating from mesoderm, play key roles in the development, homeostasis, and innate immunity of the central nervous system (CNS). Their diverse morphological characteristics are closely related to their wide range of functions. However, our knowledge of the morphophysiological attributes and interactions with neurons of microglia is limited. Exploring the correlation between microglial shape and function is a current challenge and opportunity.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Alanna G. Spiteri, Duan Ni, Zheng Lung Ling, Laurence Macia, Iain L. Campbell, Markus J. Hofer, Nicholas J. C. King
Summary: PLX5622, a widely used inhibitor of CSF-1R, has been shown to not only deplete microglia, but also mature monocytes in a mouse model of severe neuroinflammation induced by WNE. Its protective effect is mediated by the inhibition of CSF-1R, and it also has potential therapeutic applications in CNS viral infection and other monocyte-mediated diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Virology
Qiong Li, Chonglun Feng, Baolin Yang, Runze Meng, Xiaoyan Wang, Dabing Zhang
Summary: The study demonstrates the prophylactic efficacy of TMUV immune serum in protecting against TMUV-associated disease, reducing tissue injury, and decreasing TMUV levels in the periphery and central nervous system.
ARCHIVES OF VIROLOGY
(2022)
Article
Cell Biology
Ming-Kai Jhan, Chia-Ling Chen, Ting-Jing Shen, Po-Chun Tseng, Yung-Ting Wang, Rahmat Dani Satria, Chia-Yi Yu, Chiou-Feng Lin
Summary: Infection with flaviviruses can lead to neuronal damage and infiltration of inflammatory cells, resulting in viral encephalitis. Studies have shown that this is associated with polarization of M1 macrophages in the brain.
Review
Biology
Marina Alves Fontoura, Rebeca Froes Rocha, Rafael Elias Marques
Summary: Neutrophils play a crucial role in responding to infections, but their role in viral infections, especially flaviviruses, remains understudied. Flaviviruses can cause complex disease manifestations and the involvement of neutrophils in these diseases is not fully understood. Controlling the recruitment of neutrophils to flavivirus-infected tissues may reduce immunopathology and provide insights into flaviviral disease pathogenesis.
Review
Virology
Britanie M. Blackhurst, Kristen E. Funk
Summary: Flaviviruses are envelope viruses with a positive-sense RNA genome that are transmitted by arthropod vectors. Infection with these viruses can lead to neurological damage, with neuronal death and other types of cellular damage being common mechanisms.
Article
Virology
Karin Stiasny, Stefan Malafa, Stephan W. Aberle, Iris Medits, Georgios Tsouchnikas, Judith H. Aberle, Heidemarie Holzmann, Franz X. Heinz
Summary: In this study, a new IgM assay format was developed for specific diagnosis of TBE, Zika, and dengue virus infections. The IgM response proved to be highly specific for TBE and Zika infections, while cross-reactive IgM antibodies were detected in cases of primary dengue virus infections. Despite the presence of cross-reactive IgM, the assay allowed for serotype-specific diagnosis of recent dengue virus infections in most cases.
Article
Immunology
Laura Wiesner, Carla Schmutte, Imke Steffen
Summary: Tick-borne encephalitis virus (TBEV) is a serious pathogen that requires heightened biosafety measures in the laboratory. Different inactivation procedures, such as heat, acidic pH, alcohol, formaldehyde, detergents, and UV irradiation, show varying effectiveness against TBEV, depending on sample size and composition.
JOURNAL OF INFECTIOUS DISEASES
(2021)
Review
Immunology
Clayton J. Wollner, Justin M. Richner
Summary: mRNA platform allows rapid and efficient vaccine development for emerging pandemics; easy manipulation of mRNA coding region facilitates testing of novel vaccine hypotheses; diverse flaviviruses cause widespread diseases with pandemic potential, with mRNA vaccines developed against them.
Review
Oncology
Takahiro Masuda, Lukas Amann, Marco Prinz
Summary: This mini-review provides an overview of the current knowledge on the ontogenetic relationship and underlying mechanism for the establishment of CNS macrophages, highlighting their comparison with microglia.
CLINICAL AND TRANSLATIONAL MEDICINE
(2022)
Article
Virology
Paul Kinsella, Michael Moso, Genevieve Martin, Theo Karapangiotidis, Di Karamalakis, Suellen Nicholson, Mitch Batty, Kathy Jackson, Madeleine Marsland, Tilda Thomson, Lakshmi Manoharan, Helen O'brien, N. Deborah Friedman, Katherine Bond, Deborah A. Williamson, Chuan Kok Lim
Summary: This study evaluated the clinical performance of two high-throughput JEV assays in different populations and found that these assays exhibited high sensitivity and concordance in diagnosing acute infection and monitoring vaccination.
JOURNAL OF CLINICAL VIROLOGY
(2023)
Review
Cell Biology
Megumi Andoh, Ryuta Koyama
Summary: Recent studies have shown that microglia in the CNS phagocytose neuronal synapses, sparking interest among neuroscientists. Additionally, both microglia and blood-derived monocytes demonstrate phagocytic ability in the CNS parenchyma, leading to increased complexity in the study of phagocytosis in the CNS.
Article
Microbiology
Min-Goo Seo, Hak Seon Lee, Sung-Chan Yang, Byung-Eon Noh, Tae-Kyu Kim, Wook-Gyo Lee, Hee Il Lee
Summary: By collecting and monitoring mosquitoes in South Korea, this study found a minimum infection rate of flavivirus of 0.01%, with Japanese encephalitis virus detected in Culex orientalis from Sangju. Further research will help improve understanding of the risk of flavivirus infection.
Editorial Material
Clinical Neurology
Kenneth L. Tyler
ANNALS OF NEUROLOGY
(2022)
Article
Pediatrics
Kevin Messacar, Claire Palmer, LiseAnne Gregoire, Audrey Elliott, Elizabeth Ackley, Marcelo C. Perraillon, Kenneth L. Tyler, Samuel R. Dominguez
Summary: Implementation of MEP with a rapid central nervous system diagnostic stewardship program improved antimicrobial use with faster results shortening empiric therapy. Routine MEP testing for high-yield indications enables antimicrobial optimization with unchanged overall costs.
JOURNAL OF PEDIATRICS
(2022)
Article
Microbiology
Sarah Stonedahl, Jennifer Smith Leser, Penny Clarke, Kenneth L. Tyler
Summary: This study used PLX5622 to deplete microglia and investigate their role in West Nile virus infection. The results showed that microglia play a crucial role in limiting viral growth and preventing cell death, but they are not required for the cytokine/chemokine response to WNV infection.
MICROBIOLOGY SPECTRUM
(2022)
Letter
Clinical Neurology
Elizabeth Matthews, Lakshmi Chauhan, Amanda L. Piquet, Kenneth L. Tyler, Daniel M. Pastula
Review
Clinical Neurology
Jonathan D. Krett, J. David Beckham, Kenneth L. Tyler, Amanda L. Piquet, Lakshmi Chauhan, Carla J. Wallace, Daniel M. Pastula, Ronak K. Kapadia
Summary: Neurohospitalists, with their expertise in acute neurology, play a vital role in diagnosing and managing acute viral infections that affect the nervous system. This comprehensive review aims to provide practical diagnostic and therapeutic insights for busy neurohospitalists, focusing on several acute viral infections.
Article
Microbiology
Michael J. Rudy, Joshua Frost, Penny Clarke, Kenneth L. Tyler
Summary: Enterovirus D68 (EV-D68) can cause respiratory illness and paralysis. There is no known antiviral treatment for the associated paralysis, but experiments with virus-specific immunotherapy showed positive results. Therefore, early treatment is recommended for patients suspected to be infected with EV-D68 and presenting symptoms of paralysis.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2022)
Editorial Material
Clinical Neurology
Michael R. Wilson, Kenneth L. Tyler
Summary: This Viewpoint discusses the ability of next-generation sequencing to diagnose central nervous system infections, the complexity of such technology, and the need to develop programs to assist clinicians in selecting, interpreting, and responding to test results more accurately.
Review
Clinical Neurology
Kelli M. Money, T. Allen Barnett, Samuel Rapaka, Rebecca Osborn, Takashi Kitani, Daniel Fuguet, Faria Amjad, Jeffrey R. Clark, Debanjana Chakravarty, Matthew J. Copeland, Justin M. Honce, Princy N. Kumar, Rebecca N. Kumar, Fady Mousa-Ibrahim, Bilaal Sirdar, Rafal Sobota, Mengxuan Tang, Maureen K. Bolon, Eric J. Russell, Michael Wilson, Carlo Tornatore, Ayush Batra, Kenneth L. Tyler, Daniel M. Pastula
Summary: This study presents three cases of Monkeypox virus (MPXV)-associated central nervous system (CNS) disease during the 2022 outbreak, with imaging findings and treatment outcomes. The patients, previously healthy immunocompetent gay men in their 30s, developed a febrile illness followed by progressive neurologic symptoms and vesiculopustular rash. MPXV nucleic acid was detected in skin lesions of two patients, with the third patient having an epidemiological link to a confirmed case. Magnetic resonance imaging showed central spinal cord lesions and other brain abnormalities. All patients received tecovirimat treatment, and two also received immunotherapy. Good neurological recovery was observed in all cases.
ANNALS OF NEUROLOGY
(2023)
Editorial Material
Clinical Neurology
Kenneth L. L. Tyler
ANNALS OF NEUROLOGY
(2023)
Article
Virology
Sarah Stonedahl, J. Smith Leser, Penny Clarke, Huntington Potter, Timothy D. D. Boyd, Kenneth L. L. Tyler
Summary: West Nile virus (WNV) is the main cause of epidemic arboviral encephalitis in the United States. Depleting microglia in WNV-infected mice enhances viral replication and tissue injury, while augmenting microglial activation through GM-CSF administration reduces viral titers and apoptotic activity and increases survival. Stimulation of microglial activation may be a viable therapeutic approach for WNV neuroinvasive disease.
JOURNAL OF VIROLOGY
(2023)
Article
Virology
Joshua Frost, Michael J. Rudy, J. Smith Leser, Haozhou Tan, Yanmei Hu, Jun Wang, Penny Clarke, Kenneth L. Tyler
Summary: Recent outbreaks of EV-D68 in 2014, 2016, and 2018 have led to over 600 cases of a paralytic illness called AFM. AFM primarily affects children, lacks an FDA-approved treatment, and shows limited recovery from limb weakness in many patients.
JOURNAL OF VIROLOGY
(2023)
Article
Public, Environmental & Occupational Health
Daniel M. Pastula, Matthew J. Copeland, Markus C. Hannan, Samuel Rapaka, Takashi Kitani, Elizabeth Kleiner, Adrienne Showler, Cindy Yuen, Elizabeth M. Ferriman, Jennifer House, Shannon O'Brien, Alexis Burakoff, Bhavik Gupta, Kelli M. Money, Elizabeth Matthews, J. David Beckham, Lakshmi Chauhan, Amanda L. Piquet, Rebecca N. Kumar, Carlo S. Tornatore, Kia Padgett, Kevin O'Laughlin, Anil T. Mangla, Princy N. Kumar, Kenneth L. Tyler, Siobhan M. O'Connor
Summary: Monkeypox virus (MPXV) is a poxvirus that has spread to 96 countries where monkeypox was not previously reported, with most cases occurring among men who have sex with men. The current outbreak of monkeypox in the United States has shown different symptoms compared to previous outbreaks, with neuroinvasive disease being rare. This report describes two cases of encephalomyelitis in patients with monkeypox during the current U.S. outbreak. It is important to report suspected cases of neurological complications from acute MPXV infection to improve understanding and treatment options during this outbreak.
MMWR-MORBIDITY AND MORTALITY WEEKLY REPORT
(2022)
Article
Infectious Diseases
Elizabeth Matthews, J. David Beckham, Amanda L. Piquet, Kenneth L. Tyler, Lakshmi Chauhan, Daniel M. Pastula
Summary: This article reviews the eight human herpesviruses and their recent advances in relation to encephalitis, including diagnosis, treatment, complications, and management.
CURRENT TROPICAL MEDICINE REPORTS
(2022)
Article
Infectious Diseases
Lakshmi Chauhan, Elizabeth Matthews, Amanda L. Piquet, Andres Henao-Martinez, Carlos Franco-Paredes, Kenneth L. Tyler, David Beckham, Daniel M. Pastula
Summary: Environmental factors and human intervention affect the spread of arthropod vectors and the transmission cycle of arboviruses. Certain arboviral infections can result in various clinical neurologic syndromes.
CURRENT TROPICAL MEDICINE REPORTS
(2022)
Article
Microbiology
Michael J. Rudy, Christina Coughlan, Alison M. Hixon, Penny Clarke, Kenneth L. Tyler
Summary: EV-D68 can adhere to exosomes, similar to other small RNA viruses known to interact with extracellular vesicles. Uptake and infection of permissive cells by virally contaminated exosomes would have major implications in the search for the EV-D68 receptor and provide a possible route for viral entry into motor neurons. This work identifies a novel cellular entry route for EV-D68 and may facilitate the identification of genetic risk factors for development of AFM.
MICROBIOLOGY SPECTRUM
(2022)