Journal article

Sorting nexin 5 mediates virus-induced autophagy and immunity

Xiaonan Dong, Yuting Yang, Zhongju Zou, Yuting Zhao, Bo Ci, Lin Zhong, Madhura Bhave, Liwei Wang, Yi-Chun Kuo, Xiao Zang, Rui Zhong, Elizabeth R Aguilera, R Blake Richardson, Boris Simonetti, John W Schoggins, Julie K Pfeiffer, Li Yu, Xuewu Zhang, Yang Xie, Sandra L Schmid Show all

Nature | NATURE RESEARCH | Published : 2021

Abstract

Autophagy, a process of degradation that occurs via the lysosomal pathway, has an essential role in multiple aspects of immunity, including immune system development, regulation of innate and adaptive immune and inflammatory responses, selective degradation of intracellular microorganisms, and host protection against infectious diseases1,2. Autophagy is known to be induced by stimuli such as nutrient deprivation and suppression of mTOR, but little is known about how autophagosomal biogenesis is initiated in mammalian cells in response to viral infection. Here, using genome-wide short interfering RNA screens, we find that the endosomal protein sorting nexin 5 (SNX5)3,4 is essential for virus-..

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Grants

Awarded by Cancer Prevention Research Institute of Texas (CPRIT)


Awarded by NIH


Awarded by Medical Research Council (MRC)


Awarded by Wellcome Trust


Awarded by Welch Foundation


Awarded by Biotechnology and Biological Sciences Research Council


Awarded by National Health and Medical Research Council Australia (NHMRC)


Awarded by CPRIT


Funding Acknowledgements

This work was supported by Cancer Prevention Research Institute of Texas (CPRIT) grants RP120718 (B.L.) and RP180805 (Y.X.), NIH U19 AI109725 (B.L. and R.J.X.), NIH U19 AI142784 (B.L. and R.J.X.), NIH R01 DK097485 (R.J.X.), the Medical Research Council (MRC) MR/L007363/1 and MR/P018807/1 (P.J.C.), the Wellcome Trust 104568/Z/14/2 (P.J.C.), the Lister Institute of Preventive Medicine (P.J.C.), NIH R35 GM130289 (X. Zhang), NIH R01 GM115473 (Y.X.), NIH R01 CA172211 (G.X.), the Welch Foundation grant I-1702 (X. Zhang), the Rita Allen Foundation (J.W.S.) the Biotechnology and Biological Sciences Research Council grant BB/K019155/1 (N.T.K.), and National Health and Medical Research Council Australia (NHMRC) APP1163862 (P.A.G.). We thank H. W. Virgin, R. M. Sumpter Jr, A. Orvedahl, M. Packer, D. A. Leib, J. Lippincott-Schwartz, S. Tooze, S. Cherry, K. Luby-Phelps, L. N. Kinch, C. A. Brautigam, D. Tomchick, M. Roth, M. Shiloh and J. Neff for helpful discussions; M. Johnson, H. Niederstrasser and B. Posner for assistance with the siGENOME siRNA library; L. Huang for assistance with high-throughput siRNA screens and data analysis; Y. Ohashi and M. Wilson for the design of the PX domain probe and M. Manifava for assistance with PtdIns(3)P staining; A. Bugde and the UT Southwestern Medical Center (UTSW) Live Cell Imaging Facility for assistance with fluorescence microscopy; Z. Chen and Y. Li from the Structural Biology Laboratory at UTSW for assistance with cryo-EM studies (supported in part by CPRIT grant RP170644); M. S. Diamond, M. Gale Jr, A. Garcia-Sastre, D. J. Lenschow, K. Kirkegaard, M. Vignuzzi, S. Tooze, D. E. Griffin, R. J. Kuhn, I. Nakagawa, I. Bezprozvanny, M. B. Frieman, C. M. Rice and H. Wang for providing critical reagents; L. Nguyen for assistance with animal experiments; and H. Smith and H. Kang for assistance with manuscript preparation.