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Dengue Virus Type 2: Protein Binding and Active Replication in Human Central Nervous System Cells

An increased number of dengue cases with neurological complications have been reported in recent years. The lack of reliable animal models for dengue has hindered studies on dengue virus (DENV) pathogenesis and cellular tropism in vivo. We further investigate the tropism of DENV for the human centra...

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Autores principales: Salazar, Ma Isabel, Pérez-García, Marissa, Terreros-Tinoco, Marisol, Castro-Mussot, María Eugenia, Diegopérez-Ramírez, Jaime, Ramírez-Reyes, Alma Griselda, Aguilera, Penélope, Cedillo-Barrón, Leticia, García-Flores, María Martha
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3835358/
https://www.ncbi.nlm.nih.gov/pubmed/24302878
http://dx.doi.org/10.1155/2013/904067
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author Salazar, Ma Isabel
Pérez-García, Marissa
Terreros-Tinoco, Marisol
Castro-Mussot, María Eugenia
Diegopérez-Ramírez, Jaime
Ramírez-Reyes, Alma Griselda
Aguilera, Penélope
Cedillo-Barrón, Leticia
García-Flores, María Martha
author_facet Salazar, Ma Isabel
Pérez-García, Marissa
Terreros-Tinoco, Marisol
Castro-Mussot, María Eugenia
Diegopérez-Ramírez, Jaime
Ramírez-Reyes, Alma Griselda
Aguilera, Penélope
Cedillo-Barrón, Leticia
García-Flores, María Martha
author_sort Salazar, Ma Isabel
collection PubMed
description An increased number of dengue cases with neurological complications have been reported in recent years. The lack of reliable animal models for dengue has hindered studies on dengue virus (DENV) pathogenesis and cellular tropism in vivo. We further investigate the tropism of DENV for the human central nervous system (CNS), characterizing DENV interactions with cell surface proteins in human CNS cells by virus overlay protein binding assays (VOPBA) and coimmunoprecipitations. In VOPBA, three membrane proteins (60, 70, and 130 kDa) from the gray matter bound the entire virus particle, whereas only a 70 kDa protein bound in white matter. The coimmunoprecipitation assays revealed three proteins from gray matter consistently binding virus particles, one clearly distinguishable protein (~32 kDa) and two less apparent proteins (100 and 130 kDa). Monoclonal anti-NS3 targeted the virus protein in primary cell cultures of human CNS treated with DENV-2, which also stained positive for NeuH, a neuron-specific marker. Thus, our results indicate (1) that DENV-2 exhibited a direct tropism for human neurons and (2) that human neurons sustain an active DENV replication as was demonstrated by the presence of the NS3 viral antigen in primary cultures of these cells treated with DENV-2.
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spelling pubmed-38353582013-12-03 Dengue Virus Type 2: Protein Binding and Active Replication in Human Central Nervous System Cells Salazar, Ma Isabel Pérez-García, Marissa Terreros-Tinoco, Marisol Castro-Mussot, María Eugenia Diegopérez-Ramírez, Jaime Ramírez-Reyes, Alma Griselda Aguilera, Penélope Cedillo-Barrón, Leticia García-Flores, María Martha ScientificWorldJournal Research Article An increased number of dengue cases with neurological complications have been reported in recent years. The lack of reliable animal models for dengue has hindered studies on dengue virus (DENV) pathogenesis and cellular tropism in vivo. We further investigate the tropism of DENV for the human central nervous system (CNS), characterizing DENV interactions with cell surface proteins in human CNS cells by virus overlay protein binding assays (VOPBA) and coimmunoprecipitations. In VOPBA, three membrane proteins (60, 70, and 130 kDa) from the gray matter bound the entire virus particle, whereas only a 70 kDa protein bound in white matter. The coimmunoprecipitation assays revealed three proteins from gray matter consistently binding virus particles, one clearly distinguishable protein (~32 kDa) and two less apparent proteins (100 and 130 kDa). Monoclonal anti-NS3 targeted the virus protein in primary cell cultures of human CNS treated with DENV-2, which also stained positive for NeuH, a neuron-specific marker. Thus, our results indicate (1) that DENV-2 exhibited a direct tropism for human neurons and (2) that human neurons sustain an active DENV replication as was demonstrated by the presence of the NS3 viral antigen in primary cultures of these cells treated with DENV-2. Hindawi Publishing Corporation 2013-11-04 /pmc/articles/PMC3835358/ /pubmed/24302878 http://dx.doi.org/10.1155/2013/904067 Text en Copyright © 2013 Ma Isabel Salazar et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Salazar, Ma Isabel
Pérez-García, Marissa
Terreros-Tinoco, Marisol
Castro-Mussot, María Eugenia
Diegopérez-Ramírez, Jaime
Ramírez-Reyes, Alma Griselda
Aguilera, Penélope
Cedillo-Barrón, Leticia
García-Flores, María Martha
Dengue Virus Type 2: Protein Binding and Active Replication in Human Central Nervous System Cells
title Dengue Virus Type 2: Protein Binding and Active Replication in Human Central Nervous System Cells
title_full Dengue Virus Type 2: Protein Binding and Active Replication in Human Central Nervous System Cells
title_fullStr Dengue Virus Type 2: Protein Binding and Active Replication in Human Central Nervous System Cells
title_full_unstemmed Dengue Virus Type 2: Protein Binding and Active Replication in Human Central Nervous System Cells
title_short Dengue Virus Type 2: Protein Binding and Active Replication in Human Central Nervous System Cells
title_sort dengue virus type 2: protein binding and active replication in human central nervous system cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3835358/
https://www.ncbi.nlm.nih.gov/pubmed/24302878
http://dx.doi.org/10.1155/2013/904067
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