Dengue virus infection increases microglial cell migration

Jhan, Ming Kai; Tsai, Tsung‐Ting; Chen, Chia Ling; Tsai, Cheng‐Chieh; Cheng, Yi Lin; Lee, Yi Chao; Ko, Chiung Yuan; Lin, Yee Shin; Chang, Chih Peng; Lin, Liang; Lin, Chiou Feng

doi:10.1038/s41598-017-00182-z

Cited by 33 publications

(38 citation statements)

References 34 publications

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“…Asides from oncogenic viruses in the field of tumorigenesis, only a few studies have addressed virus-induced alterations of the migratory capacity of cells. In addition to dsRNA as a component of RNA virus replication complexes (as discussed for dengue virus) [ 44 ], a virus particle itself (shown for herpes simplex virus) can alter migration potential of a cell [ 45 ]. The Hazara virus as an experimental model for Crimean–Congo hemorrhagic fever virus was analyzed on Caco-2 cells in an epithelial wound healing assay [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Alterations in Cell Mechanics by Actin Cytoskeletal Changes Correlate with Strain-Specific Rubella Virus Phenotypes for Cell Migration and Induction of Apoptosis

Kräter

Sapudom

Bilz

et al. 2018

Cells

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The cellular cytoskeleton is central for key cellular functions, and as such is a marker for diseased and infected cell states. Here we analyzed infection with rubella virus (RV) strains with respect to phenotypes in cellular mechanical properties, cell movement, and viral cytopathogenicity. Real-time deformability cytometry (RT-DC), as a high-throughput platform for the assessment of cell mechanics, revealed a correlation of an increase in cortical filamentous-actin (F-actin) with a higher cellular stiffness. The additional reduction of stress fibers noted for only some RV strains as the most severe actin rearrangement lowered cell stiffness. Furthermore, a reduced collective and single cell migration speed in a wound healing assay was detected in addition to severe changes in cell morphology. The latter was followed by activation of caspase 3/7 as a sign for induction of apoptosis. Our study emphasizes RT-DC technology as a sensitive means to characterize viral cell populations and to implicate alterations of cell mechanical properties with cell functions. These interdependent events are not only promising options to elucidate viral spread and to understand viral pathologies within the infected host. They also contribute to any diseased cell state, as exemplified by RV as a representative agent for cytoskeletal alterations involved in a cytopathological outcome.

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Section: Discussionmentioning

confidence: 99%

Alterations in Cell Mechanics by Actin Cytoskeletal Changes Correlate with Strain-Specific Rubella Virus Phenotypes for Cell Migration and Induction of Apoptosis

Kräter

Sapudom

Bilz

et al. 2018

Cells

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“…The exact causal factors and specific brain cell population for causing these neurological abnormalities are not very clear yet. However, activated microglial cells have been demonstrated in DENV‐infected brain tissues . Microglia are the brain‐resident macrophages which carries out multiple innate immune responses within the central nervous system (CNS) and clear out the residuals of any nearby damaged tissues .…”

Section: Introductionmentioning

confidence: 99%

“…The actual target of DENV‐infected cells and their bystander effects in terms of neurotoxicity and brain dysfunction has not been understood very well. Although activated microglia have been observed inside DENV‐infected brains; the molecular signaling behind this DENV‐mediated microglia modulation has not been dissected …”

Section: Introductionmentioning

confidence: 99%

“…However, activated microglial cells have been demonstrated in DENV-infected brain tissues. 7 Microglia are the brain-resident macrophages which carries out multiple innate immune responses within the central nervous system (CNS) and clear out the residuals of any nearby damaged tissues. 8 Recently, DENV has been shown to infect microglial cells and cause the acute microglial inflammation suggesting their critical role in development of encephalitis.…”

Section: Introductionmentioning

confidence: 99%

“…Although activated microglia have been observed inside DENV-infected brains; the molecular signaling behind this DENV-mediated microglia modulation has not been dissected. 7 MicroRNAs have been found circulating in nearly all body fluids. Like many other viral infections, DENV is expected to modulate host cellular microRNA profile for its own benefits.…”

Section: Introductionmentioning

confidence: 99%

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Dengue NS5 modulates expression of miR‐590 to regulate ubiquitin‐specific peptidase 42 in human microglia

2019

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Dengue virus (DENV), a member of Flaviviridae family, has become neurovirulent in humans after rapid geographical expansion. Host proteasomal machinery contains both ubiquitin ligases as well as deubiquitinases (DUBs), known to influence key cellular and biological functions. MicroRNA‐mediated modulations of DUBs in case of DENV infections have not been explored yet. DENV propagation, MiRNA overexpression, miRNA knockdown, transfection, RT‐PCR, luciferase assay, and western blotting have been used in this study to establish the interaction of miR‐590 and USP42. DENV infection in human microglial cells resulted in downregulation of host DUB‐USP42 in a dose‐dependent manner and DENV‐NS5 gene alone was found to be sufficient for this downregulation. miR‐590 was upregulated upon NS5 overexpression in a dose‐dependent manner. Downregulation of USP42 was observed with miR‐590 overexpression. The specificity of this regulation was confirmed by miR‐590 mimic and anti‐miR transfections in microglial cells. miR‐590 overexpression and knockdown affected the expression level of TRAF6 in indirect manner in microglial cells. The luciferase assay demonstrated the direct regulatory interaction between miR‐590 and 3’UTR of USP42. These findings establish that DENV‐NS5 protein can potentially modulate the host deubiquitinase protein USP42 expression via altering cellular miR‐590 levels in human microglial cells.

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Neuroimmunology of rabies: New insights into an ancient disease

Bastos,

Pacheco,

Rodrigues

et al. 2023

Journal of Medical Virology

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Rabies is an ancient neuroinvasive viral (genus Lyssavirus, family Rhabdoviridae) disease affecting approximately 59,000 people worldwide. The central nervous system (CNS) is targeted, and rabies has a case fatality rate of almost 100% in humans and animals. Rabies is entirely preventable through proper vaccination, and thus, the highest incidence is typically observed in developing countries, mainly in Africa and Asia. However, there are still cases in European countries and the United States. Recently, demographic, increasing income levels, and the coronavirus disease 2019 (COVID‐19) pandemic have caused a massive raising in the animal population, enhancing the need for preventive measures (e.g., vaccination, surveillance, and animal control programs), postexposure prophylaxis, and a better understanding of rabies pathophysiology to identify therapeutic targets, since there is no effective treatment after the onset of clinical manifestations. Here, we review the neuroimmune biology and mechanisms of rabies. Its pathogenesis involves a complex and poorly understood modulation of immune and brain functions associated with metabolic, synaptic, and neuronal impairments, resulting in fatal outcomes without significant histopathological lesions in the CNS. In this context, the neuroimmunological and neurochemical aspects of excitatory/inhibitory signaling (e.g., GABA/glutamate crosstalk) are likely related to the clinical manifestations of rabies infection. Uncovering new links between immunopathological mechanisms and neurochemical imbalance will be essential to identify novel potential therapeutic targets to reduce rabies morbidity and mortality.

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Dengue virus infection increases microglial cell migration

Cited by 33 publications

References 34 publications

Alterations in Cell Mechanics by Actin Cytoskeletal Changes Correlate with Strain-Specific Rubella Virus Phenotypes for Cell Migration and Induction of Apoptosis

Alterations in Cell Mechanics by Actin Cytoskeletal Changes Correlate with Strain-Specific Rubella Virus Phenotypes for Cell Migration and Induction of Apoptosis

Dengue NS5 modulates expression of miR‐590 to regulate ubiquitin‐specific peptidase 42 in human microglia

Neuroimmunology of rabies: New insights into an ancient disease

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