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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2013
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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 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. |
repository_type |
Open Access Journal |
institution_category |
Foreign Institution |
institution |
US National Center for Biotechnology Information |
building |
NCBI PubMed |
collection |
Online Access |
language |
English |
format |
Online |
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 |
spellingShingle |
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 |
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 |
title |
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_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_sort |
dengue virus type 2: protein binding and active replication in human central nervous system cells |
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. |
publisher |
Hindawi Publishing Corporation |
publishDate |
2013 |
url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3835358/ |
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1612029231727902720 |