TY - JOUR
T1 - Dengue virus type 2
T2 - Protein binding and active replication in human central nervous system cells
AU - Salazar, Ma Isabel
AU - Pérez-García, Marissa
AU - Terreros-Tinoco, Marisol
AU - Castro-Mussot, María Eugenia
AU - Diegopérez-Ramírez, Jaime
AU - Ramírez-Reyes, Alma Griselda
AU - Aguilera, Penélope
AU - Cedillo-Barrón, Leticia
AU - García-Flores, María Martha
PY - 2013
Y1 - 2013
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84888866811&partnerID=8YFLogxK
U2 - 10.1155/2013/904067
DO - 10.1155/2013/904067
M3 - Artículo
SN - 2356-6140
VL - 2013
JO - Scientific World Journal
JF - Scientific World Journal
M1 - 904067
ER -