| First Author | Kozaki T | Year | 2015 |
| Journal | Int Immunol | Volume | 27 |
| Issue | 7 | Pages | 357-64 |
| PubMed ID | 25758257 | Mgi Jnum | J:230911 |
| Mgi Id | MGI:5766442 | Doi | 10.1093/intimm/dxv010 |
| Citation | Kozaki T, et al. (2015) Role of zinc-finger anti-viral protein in host defense against Sindbis virus. Int Immunol 27(7):357-64 |
| abstractText | 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. |
