Dengue Virus Downregulates TNFR1- and TLR3-stimulated NF-κB Activation by Targeting RIPK1

Overview

Journal Front Cell Infect Microbiol

Specialties Cell Biology
Infectious Diseases
Microbiology

Date 2022 Oct 31

PMID 36310878

Authors

Darshika J Udawatte

Diane M Lang

Jeffrey R Currier

Carey L Medin

Alan L Rothman

Affiliations

Soon will be listed here.

Abstract

Dengue virus (DENV) infection is the most prevalent arthropod-borne virus disease and is endemic in more than 100 countries. Several DENV proteins have been shown to target crucial human host proteins to evade innate immune responses and establish a productive infection. Here we report that the DENV NS3 protein targets RIPK1 (Receptor Interacting Protein Kinase I), a central mediator of inflammation and cell death, and decreases intracellular RIPK1 levels during DENV infection. The interaction of NS3 with RIPK1 results in the inhibition of NF-κB activation in response to TNFR or TLR3 stimulation. Also, we observed that the effects of NS3 on RIPK1 were independent of NS3 protease activity. Our data demonstrate a novel mechanism by which DENV suppresses normal cellular functions to evade host innate immune responses.

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