Interactions of Viral Proteins from Pathogenic and Low or Non-Pathogenic Orthohantaviruses with Human Type I Interferon Signaling.
Interactions of Viral Proteins from Pathogenic and Low or Non-Pathogenic Orthohantaviruses with Human Type I Interferon Signaling.
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DOI：
10.3390/v13010140
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发表时间：
2021-01-19
期刊：
影响因子：
--
通讯作者：
Ermonval M
中科院分区：
文献类型：
--
作者：
Gallo G;Caignard G;Badonnel K;Chevreux G;Terrier S;Szemiel A;Roman-Sosa G;Binder F;Gu Q;Da Silva Filipe A;Ulrich RG;Kohl A;Vitour D;Tordo N;Ermonval M
啮齿动物传播的正汉他病毒在其自然宿主中无症状，但它们可在人类中引起严重疾病。尽管加剧的免疫应答与汉他病毒病理学有关，但正汉他病毒必须拮抗抗病毒干扰素（IFN）应答才能在感染细胞中成功繁殖。我们研究了致病性普马拉（PUUV），低致病性图拉（TULV）和非致病性前景希尔（PHV）病毒的结构和非结构（NS）蛋白与人I型和III型IFN（IFN-I和IFN-III）途径的相互作用。三种病毒的NS蛋白均抑制RIG-I激活的IFNβ启动子，而只有PUUV的糖蛋白前体（GPC）或其切割产物Gn/Gc以及TULV的核壳（N）抑制该启动子，而且PUUV和TULV的GPC均拮抗IFN刺激的反应元件（ISRE）的启动子。因此，不同的病毒蛋白可能有助于抑制病毒背景下的IFNβ应答。虽然PUUV和TULV菌株复制相似，无论是表达完整的还是截短的NS蛋白，但只有编码野生型NS蛋白的PUUV才会导致IFN晚期表达和IFN刺激基因（ISG）的激活。这一点，与特定的结构域的NS蛋白和不同的生物过程，与细胞蛋白与NS蛋白复合物的鉴定，表明IFN-Ⅰ的激活可能不是唯一的抗病毒途径被抵消的正汉他病毒和NS蛋白可能有多种抑制功能。
Rodent-borne orthohantaviruses are asymptomatic in their natural reservoir, but they can cause severe diseases in humans. Although an exacerbated immune response relates to hantaviral pathologies, orthohantaviruses have to antagonize the antiviral interferon (IFN) response to successfully propagate in infected cells. We studied interactions of structural and nonstructural (NSs) proteins of pathogenic Puumala (PUUV), low-pathogenic Tula (TULV), and non-pathogenic Prospect Hill (PHV) viruses, with human type I and III IFN (IFN-I and IFN-III) pathways. The NSs proteins of all three viruses inhibited the RIG-I-activated IFNβ promoter, while only the glycoprotein precursor (GPC) of PUUV, or its cleavage product Gn/Gc, and the nucleocapsid (N) of TULV inhibited it. Moreover, the GPC of both PUUV and TULV antagonized the promoter of IFN-stimulated responsive elements (ISRE). Different viral proteins could thus contribute to inhibition of IFNβ response in a viral context. While PUUV and TULV strains replicated similarly, whether expressing entire or truncated NSs proteins, only PUUV encoding a wild type NSs protein led to late IFN expression and activation of IFN-stimulated genes (ISG). This, together with the identification of particular domains of NSs proteins and different biological processes that are associated with cellular proteins in complex with NSs proteins, suggested that the activation of IFN-I is probably not the only antiviral pathway to be counteracted by orthohantaviruses and that NSs proteins could have multiple inhibitory functions.
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影响因子：
5.4
作者：
Gouzil J;Fablet A;Lara E;Caignard G;Cochet M;Kundlacz C;Palmarini M;Varela M;Breard E;Sailleau C;Viarouge C;Coulpier M;Zientara S;Vitour D
通讯作者：
Vitour D
影响因子：
4.4
作者：
Blomström AL;Gu Q;Barry G;Wilkie G;Skelton JK;Baird M;McFarlane M;Schnettler E;Elliott RM;Palmarini M;Kohl A
通讯作者：
Kohl A
影响因子：
5.9
作者：
Ma, Daphne Y.;Suthar, Mehul S.
通讯作者：
Suthar, Mehul S.
影响因子：
5.4
作者：
Levine, Jessica R.;Prescott, Joseph;Feldmann, Heinz
通讯作者：
Feldmann, Heinz
影响因子：
5.4
作者：
Chauveau, Emilie;Doceul, Virginie;Vitour, Damien
通讯作者：
Vitour, Damien