A prenylated dsRNA sensor protects against severe COVID-19

Wickenhagen, Arthur, Sugrue, Elena, Lytras, Spyros, Kuchi, Srikeerthana, Noerenberg, Marko, Turnbull, Matthew L., Loney, Colin, Herder, Vanessa, Allan, Jay, Jarmson, Innes, Cameron-Ruiz, Natalia, Varjak, Margus, Pinto, Rute M., Lee, Jeffrey Y., Iselin, Louisa, Palmalux, Natasha, Stewart, Douglas G., Swingler, Simon, Greenwood, Edward J. D., Crozier, Thomas W. M., Gu, Quan, Davies, Emma L., Clohisey, Sara, Wang, Bo, Trindade Maranhão Costa, Fabio, Freire Santana, Monique, de Lima Ferreira, Luiz Carlos, Murphy, Lee, Fawkes, Angie, Meynert, Alison, Grimes, Graeme, Da Silva Filho, Joao Luiz, Marti, Matthias, Hughes, Joseph, Stanton, Richard J. ORCID: https://orcid.org/0000-0002-6799-1182, Wang, Eddie C. Y. ORCID: https://orcid.org/0000-0002-2243-4964, Ho, Antonia, Davis, Ilan, Jarrett, Ruth F., Castello, Alfredo, Robertson, David L., Semple, Malcolm G., Openshaw, Peter J. M., Palmarini, Massimo, Lehner, Paul J., Baillie, J. Kenneth, Rihn, Suzannah J., Wilson, Sam J., Baillie, J. Kenneth, Semple, Malcolm G., Openshaw, Peter J. M., Carson, Gail, Alex, Beatrice, Bach, Benjamin, Barclay, Wendy S., Bogaert, Debby, Chand, Meera, Cooke, Graham S., Docherty, Annemarie B., Dunning, Jake, da Silva Filipe, Ana, Fletcher, Tom, Green, Christopher A., Harrison, Ewen M., Ho, Antonia Ying Wai, Horby, Peter W., Ijaz, Samreen, Khoo, Saye, Klenerman, Paul, Law, Andrew, Lim, Wei Shen, Mentzer, Alexander J., Merson, Laura, Meynert, Alison M., Noursadeghi, Mahdad, Moore, Shona C., Palmarini, Massimo, Paxton, William A., Pollakis, Georgios, Price, Nicholas, Rambaut, Andrew, Robertson, David L., Russell, Clark D., Sancho-Shimizu, Vanessa, Scott, Janet T., de Silva, Thushan, Sigfrid, Louise, Solomon, Tom, Sriskandan, Shiranee, Stuart, David, Summers, Charlotte, Tedder, Richard S., Thomson, Emma C., Thompson, A. A. Roger, Thwaites, Ryan S., Turtle, Lance C. W., Gupta, Rishi K., Palmieri, Carlo, Swann, Olivia V., Zambon, Maria, Dumas, Marc-Emmanuel, Griffin, Julian L., Takats, Zoltan, Chechi, Kanta, Andrikopoulos, Petros, Osagie, Anthonia, Olanipekun, Michael, Liggi, Sonia, Lewis, Matthew R., dos Santos Correia, Gonçalo, Sands, Caroline J., Takis, Panteleimon, Maslen, Lynn, Hardwick, Hayley, Donohue, Chloe, Griffiths, Fiona, Oosthuyzen, Wilna, Donegan, Cara, Spencer, Rebecca G., Norman, Lisa, Pius, Riinu, Drake, Thomas M., Fairfield, Cameron J., Knight, Stephen R., Mclean, Kenneth A., Murphy, Derek, Shaw, Catherine A., Dalton, Jo, Girvan, Michelle, Saviciute, Egle, Roberts, Stephanie, Harrison, Janet, Marsh, Laura, Connor, Marie, Halpin, Sophie, Jackson, Clare, Gamble, Carrol, Plotkin, Daniel, Lee, James, Leeming, Gary, Law, Andrew, Wham, Murray, Clohisey, Sara, Hendry, Ross, Scott-Brown, James, Greenhalf, William, Shaw, Victoria, McDonald, Sarah E., Keating, Seán, Ahmed, Katie A., Armstrong, Jane A., Ashworth, Milton, Asiimwe, Innocent G., Bakshi, Siddharth, Barlow, Samantha L., Booth, Laura, Brennan, Benjamin, Bullock, Katie, Catterall, Benjamin W. A., Clark, Jordan J., Clarke, Emily A., Cole, Sarah, Cooper, Louise, Cox, Helen, Davis, Christopher, Dincarslan, Oslem, Dunn, Chris, Dyer, Philip, Elliott, Angela, Evans, Anthony, Finch, Lorna, Fisher, Lewis W. S., Foster, Terry, Garcia-Dorival, Isabel, Greenhalf, William, Gunning, Philip, Hartley, Catherine, Jensen, Rebecca L., Jones, Christopher B., Jones, Trevor R., Khandaker, Shadia, King, Katharine, Kiy, Robyn T., Koukorava, Chrysa, Lake, Annette, Lant, Suzannah, Latawiec, Diane, Lavelle-Langham, Lara, Lefteri, Daniella, Lett, Lauren, Livoti, Lucia A., Mancini, Maria, McDonald, Sarah, McEvoy, Laurence, McLauchlan, John, Metelmann, Soeren, Miah, Nahida S., Middleton, Joanna, Mitchell, Joyce, Moore, Shona C., Murphy, Ellen G., Penrice-Randal, Rebekah, Pilgrim, Jack, Prince, Tessa, Reynolds, Will, Ridley, P. Matthew, Sales, Debby, Shaw, Victoria E., Shears, Rebecca K., Small, Benjamin, Subramaniam, Krishanthi S., Szemiel, Agnieska, Taggart, Aislynn, Tanianis-Hughes, Jolanta, Thomas, Jordan, Trochu, Erwan, van Tonder, Libby, Wilcock, Eve, Zhang, J. Eunice, Flaherty, Lisa, Maziere, Nicole, Cass, Emily, Carracedo, Alejandra Doce, Carlucci, Nicola, Holmes, Anthony, Massey, Hannah, Murphy, Lee, Wrobel, Nicola, McCafferty, Sarah, Morrice, Kirstie, MacLean, Alan, Adeniji, Kayode, Agranoff, Daniel, Agwuh, Ken, Ail, Dhiraj, Aldera, Erin L., Alegria, Ana, Allen, Sam, Angus, Brian, Ashish, Abdul, Atkinson, Dougal, Bari, Shahedal, Barlow, Gavin, Barnass, Stella, Barrett, Nicholas, Bassford, Christopher, Basude, Sneha, Baxter, David, Beadsworth, Michael, Bernatoniene, Jolanta, Berridge, John, Berry, Colin, Best, Nicola, Bothma, Pieter, Chadwick, David, Brittain-Long, Robin, Bulteel, Naomi, Burden, Tom, Burtenshaw, Andrew, Caruth, Vikki, Chadwick, David, Chambler, Duncan, Chee, Nigel, Child, Jenny, Chukkambotla, Srikanth, Clark, Tom, Collini, Paul, Cosgrove, Catherine, Cupitt, Jason, Cutino-Moguel, Maria-Teresa, Dark, Paul, Dawson, Chris, Dervisevic, Samir, Donnison, Phil, Douthwaite, Sam, Drummond, Andrew, DuRand, Ingrid, Dushianthan, Ahilanadan, Dyer, Tristan, Evans, Cariad, Eziefula, Chi, Fegan, Chrisopher, Finn, Adam, Fullerton, Duncan, Garg, Sanjeev, Garg, Atul, Gkrania-Klotsas, Effrossyni, Godden, Jo, Goldsmith, Arthur, Graham, Clive, Hardy, Elaine, Hartshorn, Stuart, Harvey, Daniel, Havalda, Peter, Hawcutt, Daniel B., Hobrok, Maria, Hodgson, Luke, Hormis, Anil, Jacobs, Michael, Jain, Susan, Jennings, Paul, Kaliappan, Agilan, Kasipandian, Vidya, Kegg, Stephen, Kelsey, Michael, Kendall, Jason, Kerrison, Caroline, Kerslake, Ian, Koch, Oliver, Koduri, Gouri, Koshy, George, Laha, Shondipon, Laird, Steven, Larkin, Susan, Leiner, Tamas, Lillie, Patrick, Limb, James, Linnett, Vanessa, Little, Jeff, Lyttle, Mark, MacMahon, Michael, MacNaughton, Emily, Mankregod, Ravish, Masson, Huw, Matovu, Elijah, McCullough, Katherine, McEwen, Ruth, Meda, Manjula, Mills, Gary, Minton, Jane, Mirfenderesky, Mariyam, Mohandas, Kavya, Mok, Quen, Moon, James, Moore, Elinoor, Morgan, Patrick, Morris, Craig, Mortimore, Katherine, Moses, Samuel, Mpenge, Mbiye, Mulla, Rohinton, Murphy, Michael, Nagel, Megan, Nagarajan, Thapas, Nelson, Mark, Norris, Lillian, O?Shea, Matthew K., Otahal, Igor, Ostermann, Marlies, Pais, Mark, Palmieri, Carlo, Panchatsharam, Selva, Papakonstantinou, Danai, Paraiso, Hassan, Patel, Brij, Pattison, Natalie, Pepperell, Justin, Peters, Mark, Phull, Mandeep, Pintus, Stefania, Singh Pooni, Jagtur, Planche, Tim, Post, Frank, Price, David, Prout, Rachel, Rae, Nikolas, Reschreiter, Henrik, Reynolds, Tim, Richardson, Neil, Roberts, Mark, Roberts, Devender, Rose, Alistair, Rousseau, Guy, Ruge, Bobby, Ryan, Brendan, Saluja, Taranprit, Schmid, Matthias L., Shah, Aarti, Shanmuga, Prad, Sharma, Anil, Shawcross, Anna, Sizer, Jeremy, Shankar-Hari, Manu, Smith, Richard, Snelson, Catherine, Spittle, Nick, Staines, Nikki, Stambach, Tom, Stewart, Richard, Subudhi, Pradeep, Szakmany, Tamas, Tatham, Kate, Thomas, Jo, Thompson, Chris, Thompson, Robert, Tridente, Ascanio, Tupper-Carey, Darell, Twagira, Mary, Vallotton, Nick, Vancheeswaran, Rama, Vincent-Smith, Lisa, Visuvanathan, Shico, Vuylsteke, Alan, Waddy, Sam, Wake, Rachel, Walden, Andrew, Welters, Ingeborg, Whitehouse, Tony, Whittaker, Paul, Whittington, Ashley, Papineni, Padmasayee, Wijesinghe, Meme, Williams, Martin, Wilson, Lawrence, Cole, Sarah, Winchester, Stephen, Wiselka, Martin, Wolverson, Adam, Wootton, Daniel G., Workman, Andrew, Yates, Bryan and Young, Peter 2021. A prenylated dsRNA sensor protects against severe COVID-19. Science 374 (6567) , pp. 535-536. 10.1126/science.abj3624

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Additional Information:	Distributed under a Creative Commons Attribution License 4.0 (CC BY)
Publisher:	American Association for the Advancement of Science
ISSN:	0036-8075
Funders:	MRC
Date of First Compliant Deposit:	30 September 2021
Date of Acceptance:	23 September 2021
Last Modified:	23 May 2023 17:34
URI:	https://orca.cardiff.ac.uk/id/eprint/144507

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