@article{Bouhaddou_M-2023_185524,
title = {SARS-CoV-2 variants evolve convergent strategies to remodel the host response},
author = {Bouhaddou, M. and Reuschl, A. and Polacco, B. and Thorne, L. and Ummadi, M. and Ye, C. and Rosales, R. and Pelin, A. and Batra, J. and Jang, G. and Xu, J. and Moen, J. and Richards, A. and Zhou, Y. and Harjai, B. and Stevenson, E. and Rojc, A. and Ragazzini, R. and Whelan, M. and Furnon, W. and De Lorenzo, G. and Cowton, V. and Syed, A. and Ciling, A. and Deutsch, N. and Pirak, D. and Dowgier, G. and Mesner, D. and Turner, J. and McGovern, B. and Rodriguez, M. and Leiva-Rebollo, R. and Dunham, A. and Zhong, X. and Eckhardt, M. and Fossati, A. and Liotta, N. and Kehrer, T. and Cupic, A. and Rutkowska, M. and Mena, I. and Aslam, S. and Hoffert, A. and Foussard, H. and Olwal, C. and Huang, W. and Zwaka, T. and Pham, J. and Lyons, M. and Donohue, L. and Griffin, A. and Nugent, R. and Holden, K. and Deans, R. and Aviles, P. and Lopez-Martin, J. and Jimeno, J. and Obernier, K. and Fabius, J. and Soucheray, M. and Hüttenhain, R. and Jungreis, I. and Kellis, M. and Echeverria, I. and Verba, K. and Bonfanti, P. and Beltrao, P. and Sharan, R. and Doudna, J. and Martinez-Sobrido, L. and Patel, A. and Palmarini, M. and Miorin, L. and White, K. and Swaney, D. and Garcia-Sastre, A. and Jolly, C. and Zuliani-Alvarez, L. and Towers, G. and Krogan, N.},
month = {sep},
year = {2023},
abstract = {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.},
pages = {4597-4614},
volume = {186},
issue = {21},
journal = {Cell},
publisher = {Elsevier},
url = {http://dx.doi.org/10.1016/j.cell.2023.08.026},
}
