Результаты поиска

Spatial dynamics of viral replication drive biphasic lymphoid activation and systemic alphavirus immune responses.

Systemic type I interferon (IFN-I) and pro-inflammatory cytokine responses are critical for limiting mosquito-borne RNA virus viral replication and disease, yet mechanisms initiating these responses and their linkage to viral tropism for lymphoid tissues are poorly understood. Here, we reveal that virus-cell interactions and specific host signaling pathways in lymphoid tissues are determinants of systemic cytokine induction. Using Venezuelan equine encephalitis virus (VEEV) mutants with defined lymph node (LN) tropism in mice, we show that VEEV LN infection positively associates with systemic

Interferon-β and FTY720 ameliorate progressive CNS inflammation via SOCS1-associated astrocyte signaling.

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS) characterized by initially relapsing-remitting neurological deficits followed by progressive and largely irreversible disability driven by glial and neuronal pathology behind an increasingly restrictive blood–brain barrier, limiting access of peripherally applied therapeutics. Here, we show that combining sphingosine-1-phosphate receptor (S1PR) modulation with CNS-penetrant intranasal interferon-β (nIFN-β) enhances therapeutic effects relative to FTY720 alone in a chronic progressive EAE model. Co

Integrated multi-omics analysis identifies microbial and metabolic signatures and drivers of CNS autoimmunity.

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), driven by genetic and environmental determinants. The gut microbiome of people with MS (pwMS) is distinct and influences disease through immunomodulatory metabolite production. Circulating metabolites are altered in pwMS, but identifying microbial-metabolic drivers remains challenging. We previously showed that colonization by the gut commensal Limosilactobacillus reuteri exacerbates disease in the experimental autoimmune encephalomyelitis (EAE) model of MS in a tryptophan-dependent manner. Here, we integrate…

Ранние синапсовые изменения фоторецептора Mitochondria в модели мыши Множественного склероза EAE

Множественный склероз (MS) — воспалительное аутоиммунное заболевание центральной нервной системы (CNS), связанное со многими неврологическими нарушениями. Взгляд на систему часто нарушается в MS. В предыдущих исследованиях мы наблюдали ранние синусосы фоторецепторовых лент в модели мыши EAE MS, которые включали изменения в цикле синаптического везикла и нарушения предсинаптического ка2+ гомеостаза. Поскольку эти преднаптические события требуют очень много энергии, мы проанализировали, может ли синаптическая митохондрия, играющая важную роль в синаптическом энергетическом метаболизме, быть заде

Совпадение в полном тексте источника
… Induction of EAE in C57BL/6J Mice In the present study, we used the Experimental Autoimmune Encephalomyelitis (EAE) model of multiple sclerosis [ 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 ]. … Abbreviations: CFA, complete Freund’s adjuvant; MOG, myelin oligodendrocyte glycoprotein; EAE, experimental autoimmune encephalomyelitis; SDS, sodium dodecylsulfate; N = number of independent experiments; S.E.M., standard error of the mean; **, p < 0.01. …

Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy in Children: A Retrospective Analysis of 35 Cases.

OBJECTIVE: To analyze the clinical manifestations, imaging, electroencephalography, treatment, and prognosis of 35 cases of autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) in children. METHODS: Children hospitalized in the Department of Neurology, Hunan Children's Hospital, China, between January 2015 and June 2021, owing to autoimmune diseases of the central nervous system were subjected to a cell-based assay (CBA). The assay identified 40 children positive for GFAP-immunoglobulin (Ig)G antibodies in the serum and/or the cerebrospinal fluid. Based on clinical manifestation

Structure and Sequence Requirements for RNA Capping at the Venezuelan Equine Encephalitis Virus RNA 5' End.

Venezuelan equine encephalitis virus (VEEV) is a reemerging arthropod-borne virus causing encephalitis in humans and domesticated animals. VEEV possesses a positive single-stranded RNA genome capped at its 5' end. The capping process is performed by the nonstructural protein nsP1, which bears methyl and guanylyltransferase activities. The capping reaction starts with the methylation of GTP. The generated m7GTP is complexed to the enzyme to form an m7GMP-nsP1 covalent intermediate. The m7GMP is then transferred onto the 5'-diphosphate end of the viral RNA. Here, we explore the specificities of

Vascular adhesion protein-1 is actively involved in the development of inflammatory lesions in rat models of multiple sclerosis.

BACKGROUND: Vascular adhesion protein-1 (VAP-1) is an inflammation-inducible endothelial cell molecule and primary amine oxidase that mediates leukocyte entry to sites of inflammation. However, there is limited knowledge of the inflammation-related expression of VAP-1 in the central nervous system (CNS). Therefore, we investigated the expression of VAP-1 within the CNS vasculature in two focal rat models of experimental autoimmune encephalomyelitis (EAE) mimicking multiple sclerosis (MS). METHODS: EAE was induced either with Bacillus Calmette-Guérin, resulting in a delayed-type hypersensitivi…

Genome-wide association study of equine herpesvirus type 1-induced myeloencephalopathy identifies a significant single nucleotide polymorphism in a platelet-related gene.

Equine herpesvirus type 1 (EHV-1)-induced myeloencephalopathy (EHM) is a neurologic disease of horses that represents one outcome of infection. The neurologic form of disease occurs in a subset of infected horses when virus-induced endothelial cell damage triggers vasculitis and subsequent ischemic insult to the central nervous system. EHM causes considerable animal suffering and economic loss for the horse industry. Virus polymorphisms have been previously associated with disease outcome but cannot fully explain why only some horses develop EHM. This study investigated the role of host geneti

Susceptibility and Lethality of Western Equine Encephalitis Virus in Balb/c Mice When Infected by the Aerosol Route.

Western equine encephalitis virus (WEEV) naturally cycles between mosquitos and birds or rodents, with a case fatality rate of up to 15% in humans during epizootic outbreaks. There are no medical countermeasures to treat WEEV infection, and accidental aerosol exposure increases the case fatality rate up to 40%. Understanding the pathogenesis of infection is required to develop and assess medical countermeasures. This study describes the clinical and pathological findings of mice infected with WEEV by the aerosol route, and use as a model for WEEV infection in humans. Balb/c mice were infected

Confirmation of a non-synonymous SNP in PNPLA8 as a candidate causal mutation for Weaver syndrome in Brown Swiss cattle.

BACKGROUND: Bovine progressive degenerative myeloencephalopathy (Weaver syndrome) is a neurodegenerative disorder in Brown Swiss cattle that is characterized by progressive hind leg weakness and ataxia, while sensorium and spinal reflexes remain unaffected. Although the causal mutation has not been identified yet, an indirect genetic test based on six microsatellite markers and consequent exclusion of Weaver carriers from breeding have led to the complete absence of new cases for over two decades. Evaluation of disease status by imputation of 41 diagnostic single nucleotide polymorphisms (SNPs

Venezuelan equine encephalitis virus variants lacking transcription inhibitory functions demonstrate highly attenuated phenotype.

UNLABELLED: Alphaviruses represent a significant public health threat worldwide. They are transmitted by mosquitoes and cause a variety of human diseases ranging from severe meningoencephalitis to polyarthritis. To date, no efficient and safe vaccines have been developed against any alphavirus infection. However, in recent years, significant progress has been made in understanding the mechanism of alphavirus replication and virus-host interactions. These data have provided the possibility for the development of new rationally designed alphavirus vaccine candidates that combine efficient immuno

Experimental infection with equine herpesvirus type 1 (EHV-1) induces chorioretinal lesions.

Equine herpesvirus myeloencephalitis (EHM) remains one of the most devastating manifestations of equine herpesvirus type 1 (EHV-1) infection but our understanding of its pathogenesis remains rudimentary, partly because of a lack of adequate experimental models. EHV-1 infection of the ocular vasculature may offer an alternative model as EHV-1-induced chorioretinopathy appears to occur in a significant number of horses, and the pathogenesis of EHM and ocular EHV-1 may be similar. To investigate the potential of ocular EHV-1 as a model for EHM, and to determine the frequency of ocular EHV-1, our

'Multi-epitope-targeted' immune-specific therapy for a multiple sclerosis-like disease via engineered multi-epitope protein is superior to peptides.

Antigen-induced peripheral tolerance is potentially one of the most efficient and specific therapeutic approaches for autoimmune diseases. A … possible. We investigated such "multi-epitope-targeting" approach in murine experimental autoimmune encephalomyelitis (EAE) associated with a single ("classical") or multiple ("complex") anti-myelin autoreactivities, using cocktail of different encephalitogenic peptides vis-a-vis artificial multi-epitope-protein (designated Y-MSPc) encompassing rationally selected …

A humanised murine monoclonal antibody with broad serogroup specificity protects mice from challenge with Venezuelan equine encephalitis virus.

In murine models of Venezuelan equine encephalitis virus (VEEV) infection, the neutralising monoclonal antibody 1A3B-7 has been shown to be effective in passive protection from challenge by the aerosol route with serogroups I, II and Mucambo virus (formally VEE complex subtype IIIA). This antibody is able to bind to all serogroups of the VEEV complex when used in ELISA and therefore is an excellent candidate for protein engineering in order to derive a humanised molecule suitable for therapeutic use in humans. A Complementarity Determining Region (CDR) grafting approach using human germline Ig

Media attention and public perceptions of cancer and eastern equine encephalitis.

Previous research has found that members of the public have a skewed sense of health risk. The purpose of this research was to investigate how mass media use influences perceptions of threat from cancer and eastern equine encephalitis (EEE). Investigators performed a media content analysis of 253 health-related articles from 11 Massachusetts newspapers, then used logistic regression to analyze responses to a health communication survey of 613 Massachusetts adults. A greater proportion of cancer articles compared to those about EEE mentioned progress in combating the disease (61.0% vs. 16.2%, P

Treatment with cationic liposome-DNA complexes (CLDCs) protects mice from lethal Western equine encephalitis virus (WEEV) challenge.

Having recently characterized a CD-1 outbred mouse model of pathogenesis for Western equine encephalitis virus, we examined the possible protective effects of cationic liposome-DNA complexes (CLDCs) against encephalitic arboviral infection. In this investigation, mice were pre-treated, co-treated, or post-treated with CLDC then challenged with a subcutaneous or aerosol dose of the highly virulent WEEV-McMillan strain, lethal in mice 4-5 days after inoculation. Pre-treatment with CLDCs provided a significant protective effect in mice, which was reflected in significantly increased survival rate