The Timing and Magnitude of the Type I Interferon Response Are Correlated with Disease Tolerance in Arbovirus Infection.
The Timing and Magnitude of the Type I Interferon Response Are Correlated with Disease Tolerance in Arbovirus Infection.
复制标题
DOI：
10.1128/mbio.00101-23
复制
发表时间：
2023-06-27
期刊：
影响因子：
6.4
通讯作者：
Palmarini, Massimo
中科院分区：
文献类型：
--
作者：
Hardy, Alexandra;Bakshi, Siddharth;Furnon, Wilhelm;MacLean, Oscar;Gu, Quan;Varjak, Margus;Varela, Mariana;Aziz, Muhamad Afiq;Shaw, Andrew E. E.;Pinto, Rute Maria;Ruiz, Natalia Cameron;Mullan, Catrina;Taggart, Aislynn E. E.;Filipe, Ana Da Silva;Randall, Richard E. E.;Wilson, Sam J. J.;Stewart, Meredith E. E.;Palmarini, Massimo
受感染的宿主拥有两种替代策略来保护自己免受病毒感染的负面影响：抵抗力，用于消除病毒复制；以及疾病耐受性，用于在不控制病毒负荷的情况下避免组织损伤。控制病原体抗性的原理已广为人知，但有关疾病耐受性的原理却知之甚少。在这里，我们研究了引起反刍动物蓝舌病的蓝舌病毒（BTV），作为模型系统来研究与疾病耐受性相关的病毒-宿主相互作用的机制。 BTV 主要在绵羊中引起临床疾病，而牛被认为是感染宿主，尽管存在持续的病毒血症，但很少表现出临床症状。使用来自多个供体的原代细胞，我们发现绵羊细胞中的 BTV 始终比牛细胞中达到更高的滴度。 BTV 在绵羊和牛细胞中的可变复制动力学大部分是通过消除细胞 I 型干扰素 (IFN) 反应而消除的。我们确定了阻止 BTV 复制的限制因子，但这些抗病毒基因的绵羊和牛直系同源物都具有抗 BTV 特性。重要的是，我们证明，与牛细胞相比，BTV 在原代绵羊细胞中诱导宿主细胞蛋白质合成更快地关闭，从而导致抗病毒蛋白更早下调。此外，通过使用RNA测序（RNA-seq），我们还发现在BTV感染的牛细胞中干扰素刺激基因（ISG）的表达比绵羊细胞更明显。我们的数据提供了一个新的视角，了解储存库物种中的 I 型干扰素反应如何对病毒和宿主进化产生总体积极影响。
Infected hosts possess two alternative strategies to protect themselves against the negative impact of virus infections: resistance, used to abrogate virus replication, and disease tolerance, used to avoid tissue damage without controlling viral burden. The principles governing pathogen resistance are well understood, while less is known about those involved in disease tolerance. Here, we studied bluetongue virus (BTV), the cause of bluetongue disease of ruminants, as a model system to investigate the mechanisms of virus-host interactions correlating with disease tolerance. BTV induces clinical disease mainly in sheep, while cattle are considered reservoirs of infection, rarely exhibiting clinical symptoms despite sustained viremia. Using primary cells from multiple donors, we show that BTV consistently reaches higher titers in ovine cells than cells from cattle. The variable replication kinetics of BTV in sheep and cow cells were mostly abolished by abrogating the cell type I interferon (IFN) response. We identified restriction factors blocking BTV replication, but both the sheep and cow orthologues of these antiviral genes possess anti-BTV properties. Importantly, we demonstrate that BTV induces a faster host cell protein synthesis shutoff in primary sheep cells than cow cells, which results in an earlier downregulation of antiviral proteins. Moreover, by using RNA sequencing (RNA-seq), we also show a more pronounced expression of interferon-stimulated genes (ISGs) in BTV-infected cow cells than sheep cells. Our data provide a new perspective on how the type I IFN response in reservoir species can have overall positive effects on both virus and host evolution.
登录
查看更多内容
影响因子：
3.7
作者：
Smith MC;Goddard ET;Perusina Lanfranca M;Davido DJ
通讯作者：
Davido DJ
影响因子：
5.4
作者：
Caporale M;Di Gialleonorado L;Janowicz A;Wilkie G;Shaw A;Savini G;Van Rijn PA;Mertens P;Di Ventura M;Palmarini M
通讯作者：
Palmarini M
影响因子：
3.3
作者：
Dal Pozzo, F.;De Clercq, K.;Saegerman, C.
通讯作者：
Saegerman, C.
影响因子：
14.9
作者：
Gillespie M;Jassal B;Stephan R;Milacic M;Rothfels K;Senff-Ribeiro A;Griss J;Sevilla C;Matthews L;Gong C;Deng C;Varusai T;Ragueneau E;Haider Y;May B;Shamovsky V;Weiser J;Brunson T;Sanati N;Beckman L;Shao X;Fabregat A;Sidiropoulos K;Murillo J;Viteri G;Cook J;Shorser S;Bader G;Demir E;Sander C;Haw R;Wu G;Stein L;Hermjakob H;D'Eustachio P
通讯作者：
D'Eustachio P
影响因子：
5.7
作者：
Charman M;McFarlane S;Wojtus JK;Sloan E;Dewar R;Leeming G;Al-Saadi M;Hunter L;Carroll MW;Stewart JP;Digard P;Hutchinson E;Boutell C
通讯作者：
Boutell C