Peli1 facilitates virus replication and promotes neuroinflammation during West Nile virus infectionстатья из журнала
Аннотация: The E3 ubiquitin ligase Pellino 1 (Peli1) is a microglia-specific mediator of autoimmune encephalomyelitis. Its role in neurotropic flavivirus infection is largely unknown. Here, we report that mice deficient in Peli1 (Peli1-/-) were more resistant to lethal West Nile virus (WNV) infection and exhibited reduced viral loads in tissues and attenuated brain inflammation. Peli1 mediates chemokine and proinflammatory cytokine production in microglia and promotes T cell and macrophage infiltration into the CNS. Unexpectedly, Peli1 was required for WNV entry and replication in mouse macrophages and mouse and human neurons and microglia. It was also highly expressed on WNV-infected neurons and adjacent inflammatory cells from postmortem patients who died of acute WNV encephalitis. WNV passaged in Peli1-/- macrophages or neurons induced a lower viral load and impaired activation in WT microglia and thereby reduced lethality in mice. Smaducin-6, which blocks interactions between Peli1 and IRAK1, RIP1, and IKKε, did not inhibit WNV-triggered microglia activation. Collectively, our findings suggest a nonimmune regulatory role for Peli1 in promoting microglia activation during WNV infection and identify a potentially novel host factor for flavivirus cell entry and replication.
Год издания: 2018
Авторы: Huanle Luo, E. Winkelmann, Shuang Zhu, Wenjuan Ru, Elizabeth Mays, Jesus A. Silvas, Lauren L. Vollmer, Junling Gao, Bi-Hung Peng, Nathen E. Bopp, Courtney Cromer, Chao Shan, Guorui Xie, Guangyu Li, Robert B. Tesh, Vsevolod L. Popov, Pei‐Yong Shi, Shao‐Cong Sun, Ping Wu, Robyn S. Klein, Shao‐Jun Tang, Wenbo Zhang, Patricia V. Aguilar, Tian Wang
Издательство: American Society for Clinical Investigation
Источник: Journal of Clinical Investigation
Ключевые слова: Mosquito-borne diseases and control, Viral Infections and Vectors, Neuroinflammation and Neurodegeneration Mechanisms
Другие ссылки: Journal of Clinical Investigation (PDF)
Journal of Clinical Investigation (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)
Journal of Clinical Investigation (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)
Открытый доступ: bronze
Том: 128
Выпуск: 11
Страницы: 4980–4991