PUBLICATION

TNFα Impairs Rhabdoviral Clearance by Inhibiting the Host Autophagic Antiviral Response

Authors
Espín-Palazón, R., Martínez-López, A., Roca, F.J., López-Muñoz, A., Tyrkalska, S.D., Candel, S., García-Moreno, D., Falco, A., Meseguer, J., Estepa, A., Mulero, V.
ID
ZDB-PUB-160630-7
Date
2016
Source
PLoS pathogens   12: e1005699 (Journal)
Registered Authors
Mulero, Victor, Roca, Francisco Jose
Keywords
Larvae, Autophagic cell death, Zebrafish, Viral replication, Viral transmission and infection, Interferons, Gene expression, Antiviral immune response
MeSH Terms
  • Animals
  • Autophagy/physiology
  • Blotting, Western
  • Disease Models, Animal
  • Fluorescent Antibody Technique
  • Host-Parasite Interactions/immunology*
  • Organisms, Genetically Modified
  • Polymerase Chain Reaction
  • Rhabdoviridae/immunology
  • Rhabdoviridae Infections/immunology*
  • Tumor Necrosis Factor-alpha/immunology*
  • Virus Replication/physiology
  • Zebrafish
PubMed
27351838 Full text @ PLoS Pathog.
Abstract
TNFα is a pleiotropic pro-inflammatory cytokine with a key role in the activation of the immune system to fight viral infections. Despite its antiviral role, a few viruses might utilize the host produced TNFα to their benefit. Some recent reports have shown that anti-TNFα therapies could be utilized to treat certain viral infections. However, the underlying mechanisms by which TNFα can favor virus replication have not been identified. Here, a rhabdoviral infection model in zebrafish allowed us to identify the mechanism of action by which Tnfa has a deleterious role for the host to combat certain viral infections. Our results demonstrate that Tnfa signals through its receptor Tnfr2 to enhance viral replication. Mechanistically, Tnfa does not affect viral adhesion and delivery from endosomes to the cytosol. In addition, the host interferon response was also unaffected by Tnfa levels. However, Tnfa blocks the host autophagic response, which is required for viral clearance. This mechanism of action provides new therapeutic targets for the treatment of SVCV-infected fish, and advances our understanding of the previously enigmatic deleterious role of TNFα in certain viral infections.
Genes / Markers
Figures
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Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping