TY - JOUR
AU - Bouhaddou, Mehdi
AU - Reuschl, Ann-Kathrin
AU - Polacco, Benjamin J.
AU - Thorne, Lucy G.
AU - Ummadi, Manisha R.
AU - Ye, Chengjin
AU - Rosales, Romel
AU - Pelin, Adrian
AU - Batra, Jyoti
AU - Jang, Gwendolyn M.
AU - Xu, Jiewei
AU - Moen, Jack M.
AU - Richards, Alicia L.
AU - Zhou, Yuan
AU - Harjai, Bhavya
AU - Stevenson, Erica
AU - Rojc, Ajda
AU - Ragazzini, Roberta
AU - Whelan, Matthew V. X.
AU - Furnon, Wilhelm
AU - De Lorenzo, Giuditta
AU - Cowton, Vanessa M.
AU - Syed, Abdullah M.
AU - Ciling, Alison
AU - Deutsch, Noa
AU - Pirak, Daniel
AU - Dowgier, Giulia
AU - Mesner, Dejan
AU - Turner, Jane L.
AU - McGovern, Briana L.
AU - Rodriguez, M. Luis
AU - Leiva-Rebollo, Rocio
AU - Dunham, Alistair S.
AU - Zhong, Xiaofang
AU - Eckhardt, Manon
AU - Fossati, Andrea
AU - Liotta, Nicholas F.
AU - Kehrer, Thomas
AU - Cupic, Anastasija
AU - Rutkowska, Magdalena
AU - Mena, Ignacio
AU - Aslam, Sadaf
AU - Hoffert, Alyssa
AU - Foussard, Helene
AU - Olwal, Charles Ochieng'
AU - Huang, Weiqing
AU - Zwaka, Thomas
AU - Pham, John
AU - Lyons, Molly
AU - Donohue, Laura
AU - Griffin, Aliesha
AU - Nugent, Rebecca
AU - Holden, Kevin
AU - Deans, Robert
AU - Aviles, Pablo
AU - Lopez-Martin, Jose A
AU - Jimeno, Jose M
AU - Obernier, Kirsten
AU - Fabius, Jacqueline M.
AU - Soucheray, Margaret
AU - Hüttenhain, Ruth
AU - Jungreis, Irwin
AU - Kellis, Manolis
AU - Echeverria, Ignacia
AU - Verba, Kliment A.
AU - Bonfanti, Paola
AU - Beltrao, Pedro
AU - Sharan, Roded
AU - Doudna, Jennifer A.
AU - Martinez-Sobrido, Luis
AU - Patel, Arvind H.
AU - Palmarini, Massimo
AU - Miorin, Lisa
AU - White, Kris
AU - Swaney, Danielle L.
AU - Garcia-Sastre, Adolfo
AU - Jolly, Clare
AU - Zuliani-Alvarez, Lorena
AU - Towers, Greg J.
AU - Krogan, Nevan J.
PY - 2023
DA - September
TI - SARS-CoV-2 variants evolve convergent strategies to remodel the host response
JO - Cell
EP - 4614
VL - 186
IS - 21
DO - http://dx.doi.org/10.1016/j.cell.2023.08.026
AB - SARS-CoV-2 variants of concern (VOCs) emerged during the COVID-19 pandemic. Here, we used unbiased systems approaches to study the host-selective forces driving VOC evolution. We discovered that VOCs evolved convergent strategies to remodel the host by modulating viral RNA and protein levels, altering viral and host protein phosphorylation, and rewiring virus-host protein-protein interactions. Integrative computational analyses revealed that although Alpha, Beta, Gamma, and Delta ultimately converged to suppress interferon-stimulated genes (ISGs), Omicron BA.1 did not. ISG suppression correlated with the expression of viral innate immune antagonist proteins, including Orf6, N, and Orf9b, which we mapped to specific mutations. Later Omicron subvariants BA.4 and BA.5 more potently suppressed innate immunity than early subvariant BA.1, which correlated with Orf6 levels, although muted in BA.4 by a mutation that disrupts the Orf6-nuclear pore interaction. Our findings suggest that SARS-CoV-2 convergent evolution overcame human adaptive and innate immune barriers, laying the groundwork to tackle future pandemics.
PB - Elsevier
UR - https://eprints.gla.ac.uk/312216/
KW - Coronavirus (COVID-19)
ER