scholarly journals West Nile Virus-Induced Neuroinflammation: Glial Infection and Capsid Protein-Mediated Neurovirulence

2007 ◽  
Vol 81 (20) ◽  
pp. 10933-10949 ◽  
Author(s):  
Guido van Marle ◽  
Joseph Antony ◽  
Heather Ostermann ◽  
Christopher Dunham ◽  
Tracey Hunt ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
West Nile Virus ◽  
Endoplasmic Reticulum Stress ◽  
Capsid Protein ◽  
Sindbis Virus ◽  
Tissue Injury ◽  
Ex Vivo ◽  
Neuronal Loss ◽  
Gene Induction ◽  
West Nile

ABSTRACT West Nile virus (WNV) infection causes neurological disease at all levels of the neural axis, accompanied by neuroinflammation and neuronal loss, although the underlying mechanisms remain uncertain. Given the substantial activation of neuroinflammatory pathways observed in WNV infection, we hypothesized that WNV-mediated neuroinflammation and cell death occurred through WNV infection of both glia and neurons, which was driven in part by WNV capsid protein expression. Analysis of autopsied neural tissues from humans with WNV encephalomyelitis (WNVE) revealed WNV infection of both neurons and glia. Upregulation of proinflammatory genes, CXCL10, interleukin-1β, and indolamine-2′,3′-deoxygenase with concurrent suppression of the protective astrocyte-specific endoplasmic reticulum stress sensor gene, OASIS (for old astrocyte specifically induced substance), was evident in WNVE patients compared to non-WNVE controls. These findings were supported by increased ex vivo expression of these proinflammatory genes in glia infected by WNV-NY99. WNV infection caused endoplasmic reticulum stress gene induction and apoptosis in neurons but did not affect glial viability. WNV-infected astrocytic cells secreted cytotoxic factors, which caused neuronal apoptosis. The expression of the WNV-NY99 capsid protein in neurons and glia by a Sindbis virus-derived vector (SINrep5-WNVc) caused neuronal death and the release of neurotoxic factors by infected astrocytes, coupled with proinflammatory gene induction and suppression of OASIS. Striatal implantation of SINrep5-WNVC induced neuroinflammation in rats, together with the induction of CXCL10 and diminished OASIS expression, compared to controls. Moreover, magnetic resonance neuroimaging showed edema and tissue injury in the vicinity of the SINrep5-WNVc implantation site compared to controls, which was complemented by neurobehavioral abnormalities in the SINrep5-WNVc-implanted animals. These studies underscore the important interactions between the WNV capsid protein and neuroinflammation in the pathogenesis of WNV-induced neurological disorders.

scholarly journals Percutaneous muscle biopsy-induced tissue injury causes local endoplasmic reticulum stress

2018 ◽  
Vol 6 (8) ◽  
pp. e13679 ◽  
Author(s):  
Jun Yoshino ◽  
Paloma Almeda-Valdes ◽  
Anna C. Moseley ◽  
Bettina Mittendorfer ◽  
Samuel Klein
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Muscle Biopsy ◽  
Tissue Injury ◽  
Injury Causes

scholarly journals Acute Tissue Injury Caused by Subcutaneous Fat Biopsies Produces Endoplasmic Reticulum Stress

Endocrinology ◽  
2009 ◽  
Vol 150 (12) ◽  
pp. 5651-5651
Author(s):  
Guenther Boden ◽  
Matthew Silviera ◽  
Brian Smith ◽  
Peter Cheung ◽  
Carol Homko
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Tissue Injury ◽  
Subcutaneous Fat ◽  
Acute Tissue Injury

scholarly journals An ex vivo avian leukocyte culture model for West Nile virus infection

2015 ◽  
Vol 218 ◽  
pp. 19-22 ◽  
Author(s):  
Elizabeth A. Dietrich ◽  
Richard A. Bowen ◽  
Aaron C. Brault
Keyword(s):  
West Nile Virus ◽  
Virus Infection ◽  
Ex Vivo ◽  
West Nile Virus Infection ◽  
West Nile ◽  
Leukocyte Culture ◽  
Culture Model

scholarly journals ENDOPLASMIC RETICULUM STRESS IN EX VIVO HEART PERFUSION: A COMPARISON BETWEEN WORKING VERSUS NON-WORKING MODES

2017 ◽  
Vol 33 (10) ◽  
pp. S68
Author(s):  
S. Hatami ◽  
X. Qi ◽  
C. White ◽  
M. Burhani ◽  
N. Aboelnazer ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Ex Vivo ◽  
Heart Perfusion

scholarly journals Analysis of the Results of Monitoring Arbovirus Infections in the Volgograd Region in 2019

2021 ◽  
Vol 20 (1) ◽  
pp. 51-59
Author(s):  
A. O. Negodenko ◽  
E. V. Molchanova ◽  
D. R. Prilepskaya ◽  
P. Sh. Konovalov ◽  
O. A. Pavlyukova ◽  
...  
Keyword(s):  
West Nile Virus ◽  
Sindbis Virus ◽  
Hemorrhagic Fever ◽  
Virus Antigen ◽  
Farm Animals ◽  
West Nile ◽  
Hemorrhagic Fever Virus ◽  
Blood Sucking ◽  
Volgograd Region ◽  
California Serogroup

Relevance. Natural and climatic conditions, a variety of species composition of arthropods and vertebrates determine the possibility of circulation of arboviruses in the Volgograd region. The existence of natural foci of some arbovirus infections and the possibility of the formation of others suggests the need for annual monitoring of the causative agents of arbovirus diseases. Аim. Evaluation of the results of monitoring of arbovirus infections in the Volgograd region in 2019.Materials and methods: 806 blood serum samples from donors, 44 blood serum samples from febrile sick people, 300 blood serum samples from horses and 94 pools of blood-sucking mosquitoes were examined by immunofernal analysis. Result of the study of serum samples from donors in the Volgograd region, in 140 (17.4%) of 806 were found to have antibodies to the pathogen of West Nile fever (in 35 (4.3%) – IgM, in 105 (13.0%) – IgG), in 7 (2.2%) of 319 – to the Crimean hemorrhagic fever virus (in 4 (1.3%) – IgM, in 3 (0.9%) –IgG), and in 7 (2.9%) of 240 – IgG to the viruses of the California serogroup. Specific antibodies against viruses of Sindbis, Batai and Uukuniemi in the samples was not detected. The largest number of positive samples with the presence of IgG and IgM to the West Nile virus was found among residents of Volgograd (61 out of 240, 25.4%) and Volzhsky (25 out of 100, 25, 0%). Among 44 blood serums of febrile patients, 1 sample (2.3%) was found to contain an antigen of the Sindbis virus, and 2 samples (4.5%) – antigens California serogroup viruses. Specific immunoglobulins against West Nile virus were detected in 84 (28%) of 300 blood serums of farm animals (horses). In the study of 94 samples of field material (blood-sucking mosquitoes), West Nile virus antigen was detected in 14 (14.9%), Sindbis virus – in one sample (1.0%), Batai virus – in four samples (4.2%). Conclusions: the obtained results, along with the circulation of West Nile virus and Crimean hemorrhagic fever virus virus in the Volgograd region, indicate the presence of Sindbis, Batai and California serogroup viruses and necessitate further study of their role in the infectious pathology of the population.

scholarly journals Minocycline Has Anti-inflammatory Effects and Reduces Cytotoxicity in an Ex Vivo Spinal Cord Slice Culture Model of West Nile Virus Infection

2017 ◽  
Vol 91 (22) ◽  
Author(s):  
Eamon D. Quick ◽  
Scott Seitz ◽  
Penny Clarke ◽  
Kenneth L. Tyler
Keyword(s):  
Spinal Cord ◽  
West Nile Virus ◽  
Immune Cells ◽  
Microglial Activation ◽  
Macrophage Activation ◽  
Inflammatory Responses ◽  
Ex Vivo ◽  
West Nile ◽  
Expression Of Genes ◽  
Anti Inflammatory

ABSTRACT West Nile virus (WNV) is a neurotropic flavivirus that can cause significant neurological disease. Mouse models of WNV infection demonstrate that a proinflammatory environment is induced within the central nervous system (CNS) after WNV infection, leading to entry of activated peripheral immune cells. We utilized ex vivo spinal cord slice cultures (SCSC) to demonstrate that anti-inflammatory mechanisms may also play a role in WNV-induced pathology and/or recovery. Microglia are a type of macrophage that function as resident CNS immune cells. Similar to mouse models, infection of SCSC with WNV induces the upregulation of proinflammatory genes and proteins that are associated with microglial activation, including the microglial activation marker Iba1 and CC motif chemokines CCL2, CCL3, and CCL5. This suggests that microglia assume a proinflammatory phenotype in response to WNV infection similar to the proinflammatory (M1) activation that can be displayed by other macrophages. We now show that the WNV-induced expression of these and other proinflammatory genes was significantly decreased in the presence of minocycline, which has antineuroinflammatory properties, including the ability to inhibit proinflammatory microglial responses. Minocycline also caused a significant increase in the expression of anti-inflammatory genes associated with alternative anti-inflammatory (M2) macrophage activation, including interleukin 4 (IL-4), IL-13, and FIZZ1. Minocycline-dependent alterations to M1/M2 gene expression were associated with a significant increase in survival of neurons, microglia, and astrocytes in WNV-infected slices and markedly decreased levels of inducible nitric oxide synthase (iNOS). These results demonstrate that an anti-inflammatory environment induced by minocycline reduces viral cytotoxicity during WNV infection in ex vivo CNS tissue. IMPORTANCE West Nile virus (WNV) causes substantial morbidity and mortality, with no specific therapeutic treatments available. Antiviral inflammatory responses are a crucial component of WNV pathology, and understanding how they are regulated is important for tailoring effective treatments. Proinflammatory responses during WNV infection have been extensively studied, but anti-inflammatory responses (and their potential protective and reparative capabilities) following WNV infection have not been investigated. Minocycline induced the expression of genes associated with the anti-inflammatory (M2) activation of CNS macrophages (microglia) in WNV-infected SCSC while inhibiting the expression of genes associated with proinflammatory (M1) macrophage activation and was protective for multiple CNS cell types, indicating its potential use as a therapeutic reagent. This ex vivo culture system can uniquely address the ability of CNS parenchymal cells (neurons, astrocytes, and microglia) to respond to minocycline and to modulate the inflammatory environment and cytotoxicity in response to WNV infection without peripheral immune cell involvement.

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