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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Bibliographic Details
Published in:TheScientificWorld 2013-01, Vol.2013 (2013), p.1-10
Main Authors: Cedillo-Barrón, Leticia, Aguilera, Penélope, Ramírez-Reyes, Alma Griselda, Diegopérez-Ramírez, Jaime, Castro-Mussot, María Eugenia, Terreros-Tinoco, Marisol, Pérez-García, Marissa, Salazar, Ma. Isabel, García-Flores, María Martha
Format: Article
Language:English
Subjects:
Adolescent
Animal models
Antigens
Binding
Brain
Brain - virology
Brain research
Central nervous system
Child
Coma
Dengue fever
Dengue Virus - metabolism
Dengue Virus - physiology
Dengue virus type 2
Dengue viruses
Electrophoresis, Polyacrylamide Gel
Female
Genetic aspects
Health aspects
Hospitals
Humans
Immunoprecipitation
In Vitro Techniques
In vivo methods and tests
Male
Meningitis
Neurons
Pathogenesis
Protein Binding
Protein research
Proteins
Replication
Studies
Substantia alba
Tropism
Vector-borne diseases
Viral diseases
Viral proteins
Viral Proteins - metabolism
Virus Replication
Virus research
Viruses
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Summary: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.
ISSN:2356-6140
1537-744X
1537-744X
DOI:10.1155/2013/904067