NOD2 Responds to Dengue Virus Type 2 Infection in Macrophage-like Cells Interacting with MAVS Adaptor and Affecting IFN-α Production and Virus Titers

Author:

Domínguez-Martínez Diana Alhelí12ORCID,Pérez-Flores Mayra Silvia3,Núñez-Avellaneda Daniel4,Torres-Flores Jesús M.3,León-Avila Gloria5,García-Pérez Blanca Estela6ORCID,Salazar Ma Isabel3ORCID

Affiliation:

1. Laboratorio de Inmunología Celular e Inmunopatogénesis, Departamento de Inmunología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México CP 11340, Mexico

2. Unidad de Investigación en Virología y Cáncer, Hospital Infantil de México Federico Gómez, Ciudad de México CP 06720, Mexico

3. Laboratorio Nacional de Vacunología y Virus Tropicales (LNVyVT), Escuela Nacional de Ciencias Biológicas Instituto Politécnico Nacional, Ciudad de México CP 11340, Mexico

4. Dirección Adjunta de Desarrollo Tecnológico, Vinculación e Innovación, Consejo Nacional de Humanidades Ciencias y Tecnologías, Ciudad de México CP 03940, Mexico

5. Laboratorio de Genética, Departamento de Zoología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México CP 11340, Mexico

6. Laboratorio de Microbiología General, Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Ciudad de México CP 11340, Mexico

Abstract

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.

Funder

SIP-IPN

Consejo Nacional de Ciencia y Tecnología

Publisher

MDPI AG

Reference34 articles.

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