Pubblicazione scientifica

TNFα Impairs Rhabdoviral Clearance by Inhibiting the Host Autophagic Antiviral Response

FILONE TECNOLOGICO	TEMA
produzione e raccolta

RIASSUNTO

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.

DATA

Data di pubblicazione: 28/06/2016

AUTORI

ESPIN-PALAZON RAQUEL
MARTINEZ-LOPEZ ALICIA
ROCA FRANCISCO J
LOPEZ-MUNOZ AZUCENA
TYRKALSKA SYLWIA D
CANDEL SERGIO
GARCIA-MORENO DIANA
FALCO ALBERTO
MESEGUER JOSE
ESTEPA AMPARO
MULERO VICTORIANO

ENTE DI AFFERENZA

DEPARTAMENTO DE BIOLOGIA CELULAR E HISTOLOGIA FACULTAD DE BIOLOGIA UNIV MURCIA IMIB ARRIXACA MURCIA SPAIN
INST BIOLOGIA CELULAR Y MOLECULAR UNIV MIGUEL HERNANDEZ ELCHE SPAIN
UNIV PENNSYLVANIA SCHOOL OF MEDICINE US

RIVISTA

PLoS Pathogens, 12(6), e1005699

IMPACT FACTOR

6,180

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