A prenylated dsRNA sensor protects against severe COVID-19
| Title: | A prenylated dsRNA sensor protects against severe COVID-19 |
|---|---|
| Authors: | 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.; Wang, Eddie C. Y.; 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.; 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.; Paxton, William A.; Pollakis, Georgios; Price, Nicholas; Rambaut, Andrew; 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; Wham, Murray; 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; 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; 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; 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; 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; 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; Winchester, Stephen; Wiselka, Martin; Wolverson, Adam; Wootton, Daniel G.; Workman, Andrew; Yates, Bryan; Young, Peter |
| Publisher Information: | American Association for the Advancement of Science |
| Publication Year: | 2021 |
| Collection: | Cardiff University: ORCA (Online Research @ Cardiff) |
| 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: | application/pdf |
| Language: | English |
| Relation: | https://orca.cardiff.ac.uk/id/eprint/144507/1/science.abj3624.pdf; 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. https://orca.cardiff.ac.uk/view/cardiffauthors/A0697454.html orcid:0000-0002-6799-1182 orcid:0000-0002-6799-1182, Wang, Eddie C. Y. https://orca.cardiff.ac.uk/view/cardiffauthors/A047013O.html orcid:0000-0002-2243-4964 orcid: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 https://doi.org/10.1126/science.abj3624 file https://orca.cardiff.ac.uk/id/eprint/144507/1/science.abj3624.pdf |
| DOI: | 10.1126/science.abj3624 |
| Availability: | https://orca.cardiff.ac.uk/id/eprint/144507/; https://doi.org/10.1126/science.abj3624; https://orca.cardiff.ac.uk/id/eprint/144507/1/science.abj3624.pdf |
| Rights: | cc_by |
| Accession Number: | edsbas.5621A8F5 |
| Database: | BASE |