| Title: |
A prenylated dsRNA sensor protects against severe COVID-19 |
| Authors: |
Wickenhagen, A; Sugrue, E; Lytras, S; Kuchi, S; Noerenberg, M; Turnbull, ML; Loney, C; Herder, V; Allan, J; Jarmson, I; Cameron-Ruiz, N; Varjak, M; Pinto, RM; Lee, JY; Iselin, L; Palmalux, N; Stewart, DG; Swingler, S; Greenwood, EJD; Crozier, TWM; Gu, Q; Davies, EL; Clohisey, S; Wang, B; Trindade Maranhão Costa, F; Freire Santana, M; de Lima Ferreira, LC; Murphy, L; Fawkes, A; Meynert, A; Grimes, G; Da Silva Filho, JL; Marti, M; Hughes, J; Stanton, RJ; Wang, ECY; Ho, A; Davis, I; Jarrett, RF; Castello, A; Robertson, DL; Semple, MG; Openshaw, PJM; Palmarini, M; Lehner, PJ; Baillie, JK; Rihn, SJ; Wilson, SJ; ISARIC4C Investigators; Carson, G; Alex, B; Bach, B; Barclay, WS; Bogaert, D; Chand, M; Cooke, GS; Docherty, AB; Dunning, J; da Silva Filipe, A; Fletcher, T; Green, CA; Harrison, EM; Ho, AYW; Horby, PW; Ijaz, S; Khoo, S; Klenerman, P; Law, A; Lim, WS; Mentzer, AJ; Merson, L; Meynert, AM; Noursadeghi, M; Moore, SC; Paxton, WA; Pollakis, G; Price, N; Rambaut, A; Russell, CD; Sancho-Shimizu, V; Scott, JT; de Silva, T; Sigfrid, L; Solomon, T; Sriskandan, S; Stuart, D; Summers, C; Tedder, RS; Thomson, EC; Thompson, AAR; Thwaites, RS; Turtle, LCW; Gupta, RK; Palmieri, C; Swann, OV; Zambon, M; Dumas, M-E; Griffin, JL; Takats, Z; Chechi, K; Andrikopoulos, P; Osagie, A; Olanipekun, M; Liggi, S; Lewis, MR; Dos Santos Correia, G; Sands, CJ; Takis, P; Maslen, L; Hardwick, H; Donohue, C; Griffiths, F; Oosthuyzen, W; Donegan, C; Spencer, RG; Norman, L; Pius, R; Drake, TM; Fairfield, CJ; Knight, SR; Mclean, KA; Murphy, D; Shaw, CA; Dalton, J; Girvan, M; Saviciute, E; Roberts, S; Harrison, J; Marsh, L; Connor, M; Halpin, S; Jackson, C; Gamble, C; Plotkin, D; Lee, J; Leeming, G; Wham, M; Hendry, R; Scott-Brown, J; Greenhalf, W; Shaw, V; McDonald, SE; Keating, S; Ahmed, KA; Armstrong, JA; Ashworth, M; Asiimwe, IG; Bakshi, S; Barlow, SL; Booth, L; Brennan, B; Bullock, K; Catterall, BWA; Clark, JJ; Clarke, EA; Cole, S; Cooper, L; Cox, H; Davis, C; Dincarslan, O; Dunn, C; Dyer, P; Elliott, A; Evans, A; Finch, L; Fisher, LWS; Foster, T; Garcia-Dorival, I; Gunning, P; Hartley, C; Jensen, RL; Jones, CB; Jones, TR; Khandaker, S; King, K; Kiy, RT; Koukorava, C; Lake, A; Lant, S; Latawiec, D; Lavelle-Langham, L; Lefteri, D; Lett, L; Livoti, LA; Mancini, M; McDonald, S; McEvoy, L; McLauchlan, J; Metelmann, S; Miah, NS; Middleton, J; Mitchell, J; Murphy, EG; Penrice-Randal, R; Pilgrim, J; Prince, T; Reynolds, W; Ridley, PM; Sales, D; Shaw, VE; Shears, RK; Small, B; Subramaniam, KS; Szemiel, A; Taggart, A; Tanianis-Hughes, J; Thomas, J; Trochu, E; van Tonder, L; Wilcock, E; Zhang, JE; Flaherty, L; Maziere, N; Cass, E; Carracedo, AD; Carlucci, N; Holmes, A; Massey, H; Wrobel, N; McCafferty, S; Morrice, K; MacLean, A; Adeniji, K; Agranoff, D; Agwuh, K; Ail, D; Aldera, EL; Alegria, A; Allen, S; Angus, B; Ashish, A; Atkinson, D; Bari, S; Barlow, G; Barnass, S; Barrett, N; Bassford, C; Basude, S; Baxter, D; Beadsworth, M; Bernatoniene, J; Berridge, J; Berry, C; Best, N; Bothma, P; Chadwick, D; Brittain-Long, R; Bulteel, N; Burden, T; Burtenshaw, A; Caruth, V; Chambler, D; Chee, N; Child, J; Chukkambotla, S; Clark, T; Collini, P; Cosgrove, C; Cupitt, J; Cutino-Moguel, M-T; Dark, P; Dawson, C; Dervisevic, S; Donnison, P; Douthwaite, S; Drummond, A; DuRand, I; Dushianthan, A; Dyer, T; Evans, C; Eziefula, C; Fegan, C; Finn, A; Fullerton, D; Garg, S; Garg, A; Gkrania-Klotsas, E; Godden, J; Goldsmith, A; Graham, C; Hardy, E; Hartshorn, S; Harvey, D; Havalda, P; Hawcutt, DB; Hobrok, M; Hodgson, L; Hormis, A; Jacobs, M; Jain, S; Jennings, P; Kaliappan, A; Kasipandian, V; Kegg, S; Kelsey, M; Kendall, J; Kerrison, C; Kerslake, I; Koch, O; Koduri, G; Koshy, G; Laha, S; Laird, S; Larkin, S; Leiner, T; Lillie, P; Limb, J; Linnett, V; Little, J; Lyttle, M; MacMahon, M; MacNaughton, E; Mankregod, R; Masson, H; Matovu, E; McCullough, K; McEwen, R; Meda, M; Mills, G; Minton, J; Mirfenderesky, M; Mohandas, K; Mok, Q; Moon, J; Moore, E; Morgan, P; Morris, C; Mortimore, K; Moses, S; Mpenge, M; Mulla, R; Murphy, M; Nagel, M; Nagarajan, T; Nelson, M; Norris, L; O'Shea, MK; Otahal, I; Ostermann, M; Pais, M; Panchatsharam, S; Papakonstantinou, D; Paraiso, H; Patel, B; Pattison, N; Pepperell, J; Peters, M; Phull, M; Pintus, S; Singh Pooni, J; Planche, T; Post, F; Price, D; Prout, R; Rae, N; Reschreiter, H; Reynolds, T; Richardson, N; Roberts, M; Roberts, D; Rose, A; Rousseau, G; Ruge, B; Ryan, B; Saluja, T; Schmid, ML; Shah, A; Shanmuga, P; Sharma, A; Shawcross, A; Sizer, J; Shankar-Hari, M; Smith, R; Snelson, C; Spittle, N; Staines, N; Stambach, T; Stewart, R; Subudhi, P; Szakmany, T; Tatham, K; Thompson, C; Thompson, R; Tridente, A; Tupper-Carey, D; Twagira, M; Vallotton, N; Vancheeswaran, R; Vincent-Smith, L; Visuvanathan, S; Vuylsteke, A; Waddy, S; Wake, R; Walden, A; Welters, I; Whitehouse, T; Whittaker, P; Whittington, A; Papineni, P; Wijesinghe, M; Williams, M; Wilson, L; Winchester, S; Wiselka, M; Wolverson, A; Wootton, DG; Workman, A; Yates, B; Young, P |
| Publisher Information: |
American Association for the Advancement of Science |
| Publication Year: |
2021 |
| Collection: |
White Rose Research Online (Universities of Leeds, Sheffield & York) |
| Description: |
Inherited genetic factors can influence the severity of COVID-19, but the molecular explanation underpinning a genetic association is often unclear. Intracellular antiviral defenses can inhibit the replication of viruses and reduce disease severity. To better understand the antiviral defenses relevant to COVID-19, we used interferon-stimulated gene (ISG) expression screening to reveal that OAS1, through RNase L, potently inhibits SARS-CoV-2. We show that a common splice-acceptor SNP (Rs10774671) governs whether people express prenylated OAS1 isoforms that are membrane-associated and sense specific regions of SARS-CoV-2 RNAs, or only express cytosolic, nonprenylated OAS1 that does not efficiently detect SARS-CoV-2. Importantly, in hospitalized patients, expression of prenylated OAS1 was associated with protection from severe COVID-19, suggesting this antiviral defense is a major component of a protective antiviral response. |
| Document Type: |
article in journal/newspaper |
| File Description: |
text |
| Language: |
English |
| ISSN: |
0036-8075 |
| Relation: |
https://eprints.whiterose.ac.uk/id/eprint/179044/1/A%20prenylated%20dsRNA%20sensor%20protects%20against%20severe%20COVID-19.pdf; Wickenhagen, A, Sugrue, E, Lytras, S et al. (420 more authors) (2021) A prenylated dsRNA sensor protects against severe COVID-19. Science, 374 (6567). eabj3624. ISSN: 0036-8075 |
| Availability: |
https://eprints.whiterose.ac.uk/id/eprint/179044/ |
| Rights: |
cc_by_4 |
| Accession Number: |
edsbas.884B006B |
| Database: |
BASE |