期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 113, 期 8, 页码 E1034-E1043出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1516812113
关键词
KSHV; cytoplasmic LANA; cyclic GMP-AMP synthase
资金
- Deutsche Forschungsgemeinschaft (DFG) [Collaborative Research Centre] [SFB900]
- Infection Biology international PhD program of Hannover Biomedical Research School
- Helmholtz Association through the Helmholtz Virtual Institute [VH VI-424]
- Niedersachsen-Research Network on Neuroinfectiology of the Ministry of Science and Culture of Lower Saxony, Germany
The latency-associated nuclear antigen (LANA) of Kaposi sarcoma herpesvirus (KSHV) is mainly localized and functions in the nucleus of latently infected cells, playing a pivotal role in the replication and maintenance of latent viral episomal DNA. In addition, N-terminally truncated cytoplasmic isoforms of LANA, resulting from internal translation initiation, have been reported, but their function is unknown. Using coimmunoprecipitation and MS, we found the cGMP-AMP synthase (cGAS), an innate immune DNA sensor, to be a cellular interaction partner of cytoplasmic LANA isoforms. By directly binding to cGAS, LANA, and particularly, a cytoplasmic isoform, inhibit the cGAS-STING-dependent phosphorylation of TBK1 and IRF3 and thereby antagonize the cGAS-mediated restriction of KSHV lytic replication. We hypothesize that cytoplasmic forms of LANA, whose expression increases during lytic replication, inhibit cGAS to promote the reactivation of the KSHV from latency. This observation points to a novel function of the cytoplasmic isoforms of LANA during lytic replication and extends the function of LANA from its role during latency to the lytic replication cycle.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据