Nightingale, K. et al. (2022) Human cytomegalovirus protein RL1 degrades the antiviral factor SLFN11 via recruitment of the CRL4 E3 ubiquitin ligase complex. Proceedings of the National Academy of Sciences of the United States of America, 119(6), e2108173119. (doi: 10.1073/pnas.2108173119) (PMID:35105802) (PMCID:PMC8832970)
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Abstract
Human cytomegalovirus (HCMV) is an important human pathogen and a paradigm of viral immune evasion, targeting intrinsic, innate, and adaptive immunity. We have employed two orthogonal multiplexed tandem mass tag-based proteomic screens to identify host proteins down-regulated by viral factors expressed during the latest phases of viral infection. This approach revealed that the HIV-1 restriction factor Schlafen-11 (SLFN11) was degraded by the poorly characterized, late-expressed HCMV protein RL1, via recruitment of the Cullin4-RING E3 Ubiquitin Ligase (CRL4) complex. SLFN11 potently restricted HCMV infection, inhibiting the formation and spread of viral plaques. Overall, we show that a restriction factor previously thought only to inhibit RNA viruses additionally restricts HCMV. We define the mechanism of viral antagonism and also describe an important resource for revealing additional molecules of importance in antiviral innate immunity and viral immune evasion.
| Item Type: | Articles |
|---|---|
| Additional Information: | This research was funded in part by a Wellcome Trust Senior Clinical Research Fellowship 108070/Z/15/Z (to M.P.W.); Medical Research Council Project Grants MR/P001602/1 (to E.C.Y.W.) and MR/S00971X/1 and MR/V000489/1 (to R.J.S. and E.C.Y.W.); and Medical Research Council Programme Grant MC_UU_12014/3 (to A.J.D.). |
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Davison, Professor Andrew and Suarez, Dr Nicolas and Nichols, Mrs Jenna |
| Authors: | Nightingale, K., Potts, M., Hunter, L. M., Fielding, C. A., Zerbe, C. M., Fletcher-Etherington, A., Nobre, L., Wang, E. C. Y., Strang, B. L., Houghton, J. W., Antrobus, R., Suarez, N. M., Nichols, J., Davison, A. J., Stanton, R. J., and Weekes, M. P. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research |
| Journal Name: | Proceedings of the National Academy of Sciences of the United States of America |
| Publisher: | National Academy of Sciences |
| ISSN: | 0027-8424 |
| ISSN (Online): | 1091-6490 |
| Published Online: | 01 February 2022 |
| Copyright Holders: | Copyright © 2022 The Authors |
| First Published: | First published in Proceedings of the National Academy of Sciences of the United States of America 119(6): e2108173119 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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