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Niclosamide inhibits lytic replication of Epstein-Barr virus by disrupting mTOR activation.

Abstract：

:Infection with the oncogenic γ-herpesviruses Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV) cause several severe malignancies in humans. Inhibition of the lytic replication of EBV and KSHV eliminates the reservoir of persistent infection and transmission, consequently preventing the occurrence of diseases from the sources of infection. Antiviral drugs are limited in controlling these viral infectious diseases. Here, we demonstrate that niclosamide, an old anthelmintic drug, inhibits mTOR activation during EBV lytic replication. Consequently, niclosamide effectively suppresses EBV lytic gene expression, viral DNA lytic replication and virion production in EBV-infected lymphoma cells and epithelial cells. Niclosamide exhibits cytotoxicity toward lymphoma cells and induces irreversible cell cycle arrest in lytically EBV-infected cells. The ectopic overexpression of mTOR reverses the inhibition of niclosamide in EBV lytic replication. Similarly, niclosamide inhibits KSHV lytic replication. Thus, we conclude that niclosamide is a promising candidate for chemotherapy against the acute occurrence and transmission of infectious diseases of oncogenic γ-herpesviruses.

journal_name

Antiviral Res

journal_title

Antiviral research

authors

Huang L,Yang M,Yuan Y,Li X,Kuang E

doi

10.1016/j.antiviral.2016.12.002

subject

Has Abstract

pub_date

2017-02-01 00:00:00

pages

68-78

eissn

0166-3542

issn

1872-9096

pii

S0166-3542(16)30237-6

journal_volume

138

pub_type

杂志文章

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