NOD2 Responds to Dengue Virus Type 2 Infection in Macrophage-like Cells Interacting with MAVS Adaptor and Affecting IFN-α Production and Virus Titers
Diana Alhelí Domínguez-Martínez,
Mayra Silvia Pérez-Flores,
Daniel Núñez-Avellaneda,
Jesús M. Torres-Flores,
Gloria León-Avila,
Blanca Estela García-Pérez,
Ma Isabel Salazar
Affiliations
Diana Alhelí Domínguez-Martínez
Laboratorio de Inmunología Celular e Inmunopatogénesis, Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México CP 11340, Mexico
Mayra Silvia Pérez-Flores
Laboratorio Nacional de Vacunología y Virus Tropicales (LNVyVT), Escuela Nacional de Ciencias Biológicas Instituto Politécnico Nacional, Ciudad de México CP 11340, Mexico
Daniel Núñez-Avellaneda
Dirección Adjunta de Desarrollo Tecnológico, Vinculación e Innovación, Consejo Nacional de Humanidades Ciencias y Tecnologías, Ciudad de México CP 03940, Mexico
Jesús M. Torres-Flores
Laboratorio Nacional de Vacunología y Virus Tropicales (LNVyVT), Escuela Nacional de Ciencias Biológicas Instituto Politécnico Nacional, Ciudad de México CP 11340, Mexico
Gloria León-Avila
Laboratorio de Genética, Departamento de Zoología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México CP 11340, Mexico
Blanca Estela García-Pérez
Laboratorio de Microbiología General, Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México CP 11340, Mexico
Ma Isabel Salazar
Laboratorio Nacional de Vacunología y Virus Tropicales (LNVyVT), Escuela Nacional de Ciencias Biológicas Instituto Politécnico Nacional, Ciudad de México CP 11340, Mexico
In pathogen recognition, the nucleotide-binding domain (NBD) and leucine rich repeat receptors (NLRs) have noteworthy functions in the activation of the innate immune response. These receptors respond to several viral infections, among them NOD2, a very dynamic NLR, whose role in dengue virus (DENV) infection remains unclear. This research aimed to determine the role of human NOD2 in THP-1 macrophage-like cells during DENV-2 infection. NOD2 levels in DENV-2 infected THP-1 macrophage-like cells was evaluated by RT-PCR and Western blot, and an increase was observed at both mRNA and protein levels. We observed using confocal microscopy and co-immunoprecipitation assays that NOD2 interacts with the effector protein MAVS (mitochondrial antiviral signaling protein), an adaptor protein promoting antiviral activity, this occurring mainly at 12 h into the infection. After silencing NOD2, we detected increased viral loads of DENV-2 and lower levels of IFN-α in supernatants from THP-1 macrophage-like cells with NOD2 knock-down and further infected with DENV-2, compared with mock-control or cells transfected with Scramble-siRNA. Thus, NOD2 is activated in response to DENV-2 in THP-1 macrophage-like cells and participates in IFN-α production, in addition to limiting virus replication at the examined time points.
