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Nitazoxanide, an antiviral thiazolide, depletes ATP-sensitive intracellular Ca(2+) stores.

Identifieur interne : 000F14 ( Main/Exploration ); précédent : 000F13; suivant : 000F15

Nitazoxanide, an antiviral thiazolide, depletes ATP-sensitive intracellular Ca(2+) stores.

Auteurs : Omodele Ashiru [Royaume-Uni] ; Jonathon D. Howe [Royaume-Uni] ; Terry D. Butters [Royaume-Uni]

Source :

RBID : pubmed:24971706

Descripteurs français

English descriptors

Abstract

Nitazoxanide (NTZ) inhibits influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication but effects on the replication of other members of the Flaviviridae family has yet to be defined. The pestivirus bovine viral diarrhoea virus (BVDV) is a surrogate model for HCV infection and NTZ induced PKR and eIF2α phosphorylation in both uninfected and BVDV-infected cells. This led to the observation that NTZ depletes ATP-sensitive intracellular Ca(2+) stores. In addition to PKR and eIF2α phosphorylation, consequences of NTZ-mediated Ca(2+) mobilisation included induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking. To adapt to NTZ-mediated ER stress, NTZ treated cells upregulated translation of Ca(2+)-binding proteins, including the ER chaperone Bip and the cytosolic pro-survival and anti-viral protein TCTP. Depletion of intracellular Ca(2+) stores is the primary consequence of NTZ treatment and is likely to underpin all antiviral mechanisms attributed to the thiazolide.

DOI: 10.1016/j.virol.2014.05.015
PubMed: 24971706


Affiliations:


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<div type="abstract" xml:lang="en">Nitazoxanide (NTZ) inhibits influenza, Japanese encephalitis, hepatitis B and hepatitis C virus replication but effects on the replication of other members of the Flaviviridae family has yet to be defined. The pestivirus bovine viral diarrhoea virus (BVDV) is a surrogate model for HCV infection and NTZ induced PKR and eIF2α phosphorylation in both uninfected and BVDV-infected cells. This led to the observation that NTZ depletes ATP-sensitive intracellular Ca(2+) stores. In addition to PKR and eIF2α phosphorylation, consequences of NTZ-mediated Ca(2+) mobilisation included induction of chronic sub-lethal ER stress as well as perturbation of viral protein N-linked glycosylation and trafficking. To adapt to NTZ-mediated ER stress, NTZ treated cells upregulated translation of Ca(2+)-binding proteins, including the ER chaperone Bip and the cytosolic pro-survival and anti-viral protein TCTP. Depletion of intracellular Ca(2+) stores is the primary consequence of NTZ treatment and is likely to underpin all antiviral mechanisms attributed to the thiazolide. </div>
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