Infection with a Brazilian isolate of Zika virus generates RIG-I stimulatory RNA and the viral NS5 protein blocks type I IFN induction and signaling.
Infection with a Brazilian isolate of Zika virus generates RIG-I stimulatory RNA and the viral NS5 protein blocks type I IFN induction and signaling.
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DOI：
10.1002/eji.201847483
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发表时间：
2018-07
影响因子：
5.4
通讯作者：
Rehwinkel J
中科院分区：
文献类型：
--
作者：
Hertzog J;Dias Junior AG;Rigby RE;Donald CL;Mayer A;Sezgin E;Song C;Jin B;Hublitz P;Eggeling C;Kohl A;Rehwinkel J
寨卡病毒（ZIKV）是美国的一个主要公共卫生问题。我们报道了ZIKV感染和从ZIKV感染的细胞中提取的RNA有效地激活了I型干扰素（IFN）的诱导。这种作用完全依赖于线粒体抗病毒信号蛋白（MAVS），暗示RIG-I-样受体（RLR）是病毒RNA的上游传感器。事实上，RIG-I和相关的RNA传感器MDA 5有助于响应于来自感染细胞的RNA的I型IFN诱导。我们发现，来自最近巴西分离株的ZIKV NS 5阻断了TLR下游的I型IFN诱导，并且还抑制了I型IFN受体（IFNAR）信号传导。我们定义了ZIKV NS 5核定位信号，并报道了抑制IFNAR下游的信号传导不需要NS 5核定位。从机制上讲，NS 5通过导致STAT 2水平降低和阻断STAT 1磷酸化来阻断IFNAR信号传导，STAT 1是由I型IFN激活的两种转录因子。综上所述，我们的观察结果表明ZIKV感染经由TLR诱导I型IFN应答，并且ZIKV通过阻断TLR和IFNAR下游的信号传导来干扰该应答。
Zika virus (ZIKV) is a major public health concern in the Americas. We report that ZIKV infection and RNA extracted from ZIKV infected cells potently activated the induction of type I interferons (IFNs). This effect was fully dependent on the mitochondrial antiviral signaling protein (MAVS), implicating RIG‐I‐like receptors (RLRs) as upstream sensors of viral RNA. Indeed, RIG‐I and the related RNA sensor MDA5 contributed to type I IFN induction in response to RNA from infected cells. We found that ZIKV NS5 from a recent Brazilian isolate blocked type I IFN induction downstream of RLRs and also inhibited type I IFN receptor (IFNAR) signaling. We defined the ZIKV NS5 nuclear localization signal and report that NS5 nuclear localization was not required for inhibition of signaling downstream of IFNAR. Mechanistically, NS5 blocked IFNAR signaling by both leading to reduced levels of STAT2 and by blocking phosphorylation of STAT1, two transcription factors activated by type I IFNs. Taken together, our observations suggest that ZIKV infection induces a type I IFN response via RLRs and that ZIKV interferes with this response by blocking signaling downstream of RLRs and IFNAR.
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DOI：
10.3390/v7082837
发表时间：
2015-08-13
期刊：
Viruses
影响因子：
--
作者：
Klema VJ;Padmanabhan R;Choi KH
通讯作者：
Choi KH
DOI：
10.1126/science.aaf5036
发表时间：
2016-04-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Faria NR;Azevedo RDSDS;Kraemer MUG;Souza R;Cunha MS;Hill SC;Thézé J;Bonsall MB;Bowden TA;Rissanen I;Rocco IM;Nogueira JS;Maeda AY;Vasami FGDS;Macedo FLL;Suzuki A;Rodrigues SG;Cruz ACR;Nunes BT;Medeiros DBA;Rodrigues DSG;Queiroz ALN;da Silva EVP;Henriques DF;da Rosa EST;de Oliveira CS;Martins LC;Vasconcelos HB;Casseb LMN;Simith DB;Messina JP;Abade L;Lourenço J;Alcantara LCJ;de Lima MM;Giovanetti M;Hay SI;de Oliveira RS;Lemos PDS;de Oliveira LF;de Lima CPS;da Silva SP;de Vasconcelos JM;Franco L;Cardoso JF;Vianez-Júnior JLDSG;Mir D;Bello G;Delatorre E;Khan K;Creatore M;Coelho GE;de Oliveira WK;Tesh R;Pybus OG;Nunes MRT;Vasconcelos PFC
通讯作者：
Vasconcelos PFC
通过RIG-I介导的5'-二磷酸RNA识别的抗病毒药免疫。
影响因子：
64.8
作者：
Goubau, Delphine;Schlee, Martin;Deddouche, Safia;Pruijssers, Andrea J.;Zillinger, Thomas;Goldeck, Marion;Schuberth, Christine;Van der Veen, Annemarthe G.;Fujimura, Tsutomu;Rehwinkel, Jan;Iskarpatyoti, Jason A.;Barchet, Winfried;Ludwig, Janos;Dermody, Terence S.;Hartmann, Gunther;Reis e Sousa, Caetano
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Reis e Sousa, Caetano
病毒逃避干扰素的十种策略。
影响因子：
30.3
作者：
García-Sastre A
通讯作者：
García-Sastre A
影响因子：
3.4
作者：
Cumberworth SL;Clark JJ;Kohl A;Donald CL
通讯作者：
Donald CL