a-murine-model-dengue-virus-induced-acute-viral-encephalitis-like

A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease

Dengue virus (DENV), an arthropod-borne virus transmitted by mosquitoes, may cause the severe disease known as dengue hemorrhagic fever, which is ...

transtubular-endoscopic-posterolateral-decompression-for-l5-s1-lumbar

Transtubular Endoscopic Posterolateral Decompression for L5-S1 Lumbar Lateral Disc Herniation

We report a novel technique for C-arm free transtubular L5 nerve decompression under CT-based navigation to reduce the radiation hazard. This procedure is ...

Taipei Medical University

Chang Gung University

Dengue virus (DENV) infection in neuronal cells was speculated to trigger neuropathy. Herein, we determined the blockade of DENV infection by targeting endocytic pathways in vitro and in vivo. In DENV-infected mouse brains, we previously showed that viral proteins are expressed in neuronal cells around the hippocampus with accompanying neurotoxicity. DENV caused infection, including entry, double-stranded (ds)RNA replication, protein expression, and virus release, followed by cytotoxicity in the mouse neuronal Neuro-2a cell line. Pharmacologically blocking clathrin-mediated endocytosis of the DENV retarded viral replication. Targeting vacuolar-type H-ATPase (V-ATPase)-based endosomal acidification effectively blocked the DENV replication process, but had no direct effect on viral translation. Blockade of the clathrin- and V-ATPase-based endocytic pathways also attenuated DENV-induced neurotoxicity. Inhibiting endosomal acidification effectively retarded DENV infection, acute viral encephalitis, and mortality. These results demonstrate that clathrin mediated endocytosis of DENV followed by endosomal acidification-dependent viral replication in neuronal cells, which can lead to neurotoxicity.

Blockade of dengue virus infection and viral cytotoxicity in neuronal cells in vitro and in vivo by targeting endocytic pathways.

Proinflammatory TNF-α facilitates dengue virus (DENV) infection in endovascular dysfunction and neurotoxicity. The introduction of TNF-α blocking therapy with Abs is performed to test its therapeutic effect in this study. In DENV-infected mice, TNF-α production in the brain accompanied the progression of neurotoxicity and encephalitis. DENV infection caused the loss of hippocampal neurons with TNF-α expression around damaged regions, and immunostaining showed the induction of apoptosis in hippocampal neurons. TNF-α was expressed in active microglia and astrocytes in DENV-infected mice. TNF-α facilitated DENV-induced neurotoxicity in vitro in murine Neuro-2a cells. Using a currently established encephalitic mouse model in which DENV infection causes progressive hunchback posture, limbic seizures, limbic weakness, paralysis, and lethality 7 days postinfection, we showed that TNF-α transgenic mice represented the progressive disease development and administration of neutralizing TNF-α Ab reduced dengue encephalitis and mortality. These results demonstrate an immunopathogenesis of TNF-α for mediating DENV-induced encephalitis-associated neurotoxicity and that targeting TNF-α can be used as a strategy against dengue encephalitis.

Anti-TNF-α restricts dengue virus-induced neuropathy.

The antiparasitic agent niclosamide has been demonstrated to inhibit the arthropod-borne Zika virus. Here, we investigated the antiviral capacity of niclosamide against dengue virus (DENV) serotype 2 infection in vitro and in vivo.

Tsung-Ting Tsai

Graduate Institute of Medical Sciences,
College of Medicine,
Department of Microbiology and Immunology,
School of Medicine

Taipei Medical University

A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease

Transtubular Endoscopic Posterolateral Decompression for L5-S1 Lumbar Lateral Disc Herniation

Tsung-Ting Tsai

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Graduate Institute of Medical Sciences,College of Medicine,Department of Microbiology and Immunology,School of Medicine

Taipei Medical University

A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease

Transtubular Endoscopic Posterolateral Decompression for L5-S1 Lumbar Lateral Disc Herniation

Graduate Institute of Medical Sciences,
College of Medicine,
Department of Microbiology and Immunology,
School of Medicine