Role of zinc-finger anti-viral protein in host defense against Sindbis virus

International Immunology
Tatsuya KozakiTatsuya Saitoh

Abstract

Accumulating evidence indicates that type I interferon (IFN) mediates the host protective response to RNA viruses. However, the anti-viral effector molecules involved in this response have not been fully identified. Here, we show that zinc-finger anti-viral protein (ZAP), an IFN-inducible gene, plays a critical role in the elimination of Sindbis virus (SINV) in vitro and in vivo. The loss of ZAP greatly enhances the replication of SINV but does not inhibit type I IFN production in primary mouse embryonic fibroblasts (MEFs). ZAP binds and destabilizes SINV RNA, thereby suppressing the replication of SINV. Type I IFN fails to suppress SINV replication in ZAP-deficient MEFs, whereas the ectopic expression of ZAP is sufficient to suppress the replication of SINV in MEFs lacking the expression of type I IFN and the IFN-inducible genes. ZAP-deficient mice are highly susceptible to SINV infection, although they produce sufficient amounts of type I IFN. Therefore, ZAP is an RNA-sensing anti-viral effector molecule that mediates the type-I-IFN-dependent host defense against SINV.

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Citations

Sep 24, 2015·BMC Evolutionary Biology·Jeffrey P Vedanayagam, Daniel Garrigan
Oct 30, 2016·Journal of Virology·Xinlu WangGuangxia Gao
Feb 8, 2020·Genes & Development·Anthony R FehrMasanori Aikawa
Aug 29, 2018·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Victoria K Baxter, Mark T Heise
Oct 17, 2018·Proceedings of the National Academy of Sciences of the United States of America·Rachy AbrahamDiane E Griffin
Feb 19, 2017·Proceedings of the National Academy of Sciences of the United States of America·Tatsuya KozakiTatsuya Saitoh
Jan 24, 2021·Trends in Microbiology·Huifang Zhu, Chunfu Zheng
Apr 4, 2021·Viruses·Mathilde MalgrasNicolas Lévêque
Jun 16, 2021·Annual Review of Virology·Mattia FicarelliChad M Swanson

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