Gammaherpesvirus Usurps Host IL-17 Signaling To Support the Establishment of Chronic Infection.
Gammaherpesvirus Usurps Host IL-17 Signaling To Support the Establishment of Chronic Infection.
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DOI：
10.1128/mbio.00566-21
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发表时间：
2021-04-06
期刊：
影响因子：
6.4
通讯作者：
Tarakanova VL
中科院分区：
文献类型：
--
作者：
Jondle CN;Johnson KE;Aurubin C;Sylvester P;Xin G;Cui W;Huppler AR;Tarakanova VL
伽玛疱疹病毒在大多数人中造成终生感染，并与 B 细胞淋巴瘤有关。 IL-17A 是一种宿主细胞因子，在清除细菌和真菌感染中发挥着明确的作用；然而，人们对 IL-17A 在病毒感染中的作用知之甚少。伽马疱疹病毒可造成终生感染，并与多种癌症有关，包括 B 细胞淋巴瘤。这些病毒操纵 B 细胞分化过程，在记忆 B 细胞中建立终身感染。具体来说，伽马疱疹病毒感染幼稚 B 细胞，并促进受感染和未感染的幼稚 B 细胞进入生发中心，其中病毒侵占生发中心 B 细胞的快速增殖，以指数方式增加其细胞潜伏库。除了促进潜伏感染的建立外，生发中心 B 细胞还被认为是病毒转化的目标。在这项研究中，我们发现了宿主白细胞介素 17A (IL-17A) 的一种新的前病毒作用，这是一种公认的抗菌和抗真菌因子。 IL-17A信号传导的缺失以接种依赖性方式减弱了慢性伽马疱疹病毒感染的建立和伽马疱疹病毒驱动的生发中心反应。此外，IL-17A 治疗直接支持伽玛疱疹病毒再激活和从头溶解感染。这项研究首次证明了 IL-17 信号转导的多方面原病毒作用。
Gammaherpesviruses establish lifelong infections in a majority of humans and are associated with B cell lymphomas. IL-17A is a host cytokine that plays a well-established role in the clearance of bacterial and fungal infections; however, the role of IL-17A in viral infections is poorly understood. Gammaherpesviruses establish lifelong infection and are associated with a variety of cancers, including B cell lymphomas. These viruses manipulate the B cell differentiation process to establish lifelong infection in memory B cells. Specifically, gammaherpesviruses infect naive B cells and promote entry of both infected and uninfected naive B cells into germinal centers, where the virus usurps rapid proliferation of germinal center B cells to exponentially increase its cellular latent reservoir. In addition to facilitating the establishment of latent infection, germinal center B cells are thought to be the target of viral transformation. In this study, we have uncovered a novel proviral role of host interleukin 17A (IL-17A), a well-established antibacterial and antifungal factor. Loss of IL-17A signaling attenuated the establishment of chronic gammaherpesvirus infection and gammaherpesvirus-driven germinal center response in a route of inoculation-dependent manner. Further, IL-17A treatment directly supported gammaherpesvirus reactivation and de novo lytic infection. This study is the first demonstration of a multifaceted proviral role of IL-17 signaling.
DOI：
10.4049/jimmunol.1201407
发表时间：
2012-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Getahun A;Smith MJ;Kogut I;van Dyk LF;Cambier JC
通讯作者：
Cambier JC