Dengue virus type 2: protein binding and active replication in human central nervous system cells

Area of Science:

• Neuroscience
• Virology
• Immunology

Background:

• Recent years have seen a rise in dengue cases with neurological complications.
• The absence of effective animal models impedes research into dengue virus (DENV) pathogenesis and in vivo cellular tropism.

Purpose of the Study:

• To investigate DENV tropism within the human central nervous system (CNS).
• To characterize DENV interactions with cell surface proteins in human CNS cells.

Main Methods:

• Virus overlay protein binding assays (VOPBA) were used to identify protein interactions.
• Coimmunoprecipitation assays were performed to confirm binding proteins.
• Primary human CNS cell cultures were treated with DENV-2 and stained for viral proteins and neuron markers.

Main Results:

• VOPBA identified membrane proteins (60, 70, 130 kDa) in gray matter and a 70 kDa protein in white matter that bound DENV.
• Coimmunoprecipitation revealed three gray matter proteins (~32, 100, 130 kDa) binding DENV.
• DENV-2 infected human neurons, with NS3 viral antigen detected, indicating active replication.

Conclusions:

• DENV-2 demonstrates direct tropism for human neurons.
• Human neurons support active DENV replication, evidenced by NS3 viral antigen presence.