{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T17:02:43Z","timestamp":1793638963618,"version":"4.5.1"},"reference-count":50,"publisher":"Springer Science and Business Media LLC","issue":"7896","license":[{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nature"],"published-print":{"date-parts":[[2022,2,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    During the current coronavirus disease 2019 (COVID-19) pandemic, a variety of mutations have accumulated in the viral genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and, at the time of writing, four variants of concern are considered to be potentially hazardous to human society\n                    <jats:sup>1<\/jats:sup>\n                    . The recently emerged B.1.617.2\/Delta variant of concern is closely associated with the COVID-19 surge that occurred in India in the\u00a0spring of\u00a02021 (ref.\n                    <jats:sup>2<\/jats:sup>\n                    ). However, the virological properties of B.1.617.2\/Delta remain unclear. Here we show that the B.1.617.2\/Delta variant is highly fusogenic and notably more pathogenic than prototypic SARS-CoV-2 in infected hamsters. The P681R mutation in the spike protein, which is highly conserved in this lineage, facilitates cleavage of the spike protein and enhances viral fusogenicity. Moreover, we demonstrate that the P681R-bearing virus exhibits higher pathogenicity compared with its parental virus. Our data suggest that the P681R mutation is a hallmark of the virological phenotype of the B.1.617.2\/Delta variant and is associated with enhanced pathogenicity.\n                  <\/jats:p>","DOI":"10.1038\/s41586-021-04266-9","type":"journal-article","created":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T12:03:14Z","timestamp":1637841794000},"page":"300-306","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":609,"title":["Enhanced fusogenicity and pathogenicity of SARS-CoV-2 Delta P681R mutation"],"prefix":"10.1038","volume":"602","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2792-4399","authenticated-orcid":false,"given":"Akatsuki","family":"Saito","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3765-8482","authenticated-orcid":false,"given":"Takashi","family":"Irie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rigel","family":"Suzuki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Maemura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9163-1665","authenticated-orcid":false,"given":"Hesham","family":"Nasser","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiya","family":"Uriu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Kosugi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7469-1276","authenticated-orcid":false,"given":"Kotaro","family":"Shirakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0541-706X","authenticated-orcid":false,"given":"Kenji","family":"Sadamasu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izumi","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0440-8321","authenticated-orcid":false,"given":"Jumpei","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaqi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8266-020X","authenticated-orcid":false,"given":"Kiyoko","family":"Iwatsuki-Horimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mutsumi","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7768-5157","authenticated-orcid":false,"given":"Seiya","family":"Yamayoshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha","family":"Loeber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5400-5905","authenticated-orcid":false,"given":"Masumi","family":"Tsuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6145-395X","authenticated-orcid":false,"given":"Lei","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1764-2937","authenticated-orcid":false,"given":"Seiya","family":"Ozono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7633-7238","authenticated-orcid":false,"given":"Erika P.","family":"Butlertanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9866-4398","authenticated-orcid":false,"given":"Yuri L.","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryo","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3825-7018","authenticated-orcid":false,"given":"Kenta","family":"Shimizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0062-2753","authenticated-orcid":false,"given":"Kumiko","family":"Yoshimatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoko","family":"Kawabata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3754-1252","authenticated-orcid":false,"given":"Takemasa","family":"Sakaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2625-5322","authenticated-orcid":false,"given":"Kenzo","family":"Tokunaga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isao","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2572-6786","authenticated-orcid":false,"given":"Hiroyuki","family":"Asakura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8069-9250","authenticated-orcid":false,"given":"Mami","family":"Nagashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1046-8286","authenticated-orcid":false,"given":"Yasuhiro","family":"Kazuma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryosuke","family":"Nomura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihito","family":"Horisawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhisa","family":"Yoshimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7678-4284","authenticated-orcid":false,"given":"Akifumi","family":"Takaori-Kondo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Imai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"The Genotype to Phenotype Japan (G2P-Japan) Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika","family":"Chiba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirotake","family":"Furihata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruyo","family":"Hasebe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuko","family":"Kitazato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruko","family":"Kubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoko","family":"Misawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nanami","family":"Morizako","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kohei","family":"Noda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Oide","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Suganami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyoko","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kana","family":"Tsushima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miyabishara","family":"Yokoyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6470-3301","authenticated-orcid":false,"given":"Shinya","family":"Tanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1760-3839","authenticated-orcid":false,"given":"So","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2869-9450","authenticated-orcid":false,"given":"Terumasa","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5471-8331","authenticated-orcid":false,"given":"Takasuke","family":"Fukuhara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5061-8296","authenticated-orcid":false,"given":"Yoshihiro","family":"Kawaoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4431-1380","authenticated-orcid":false,"given":"Kei","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,25]]},"reference":[{"key":"4266_CR1","unstructured":"Coronavirus Disease 2019 (WHO, 2021); https:\/\/www.who.int\/emergencies\/diseases\/novel-coronavirus-2019"},{"key":"4266_CR2","doi-asserted-by":"publisher","first-page":"1131","DOI":"10.1038\/s41591-021-01397-4","volume":"27","author":"J Singh","year":"2021","unstructured":"Singh, J., Rahman, S. A., Ehtesham, N. Z., Hira, S. & Hasnain, S. E. SARS-CoV-2 variants of concern are emerging in India. Nat. Med. 27, 1131\u20131133 (2021).","journal-title":"Nat. Med."},{"key":"4266_CR3","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1016\/j.chom.2021.02.020","volume":"29","author":"JA Plante","year":"2021","unstructured":"Plante, J. A. et al. The variant gambit: COVID\u2019s next move. Cell Host Microbe 29, 508\u2013515 (2021).","journal-title":"Cell Host Microbe"},{"key":"4266_CR4","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1016\/j.cell.2020.06.043","volume":"182","author":"B Korber","year":"2020","unstructured":"Korber, B. et al. Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell 182, 812\u2013827 (2020).","journal-title":"Cell"},{"key":"4266_CR5","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1038\/s41586-021-03361-1","volume":"592","author":"B Zhou","year":"2021","unstructured":"Zhou, B. et al. SARS-CoV-2 spike D614G change enhances replication and transmission. Nature 592, 122\u2013127 (2021).","journal-title":"Nature"},{"key":"4266_CR6","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21118-2","volume":"12","author":"S Ozono","year":"2021","unstructured":"Ozono, S. et al. SARS-CoV-2 D614G spike mutation increases entry efficiency with enhanced ACE2-binding affinity. Nat. Commun. 12, 848 (2021).","journal-title":"Nat. Commun."},{"key":"4266_CR7","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/j.cell.2020.09.032","volume":"183","author":"L Yurkovetskiy","year":"2020","unstructured":"Yurkovetskiy, L. et al. Structural and functional analysis of the D614G SARS-CoV-2 spike protein variant. Cell 183, 739\u2013751 (2020).","journal-title":"Cell"},{"key":"4266_CR8","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1126\/science.abe8499","volume":"370","author":"YJ Hou","year":"2020","unstructured":"Hou, Y. J. et al. SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo. Science 370, 1464\u20131468 (2020).","journal-title":"Science"},{"key":"4266_CR9","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1038\/s41586-020-2895-3","volume":"592","author":"JA Plante","year":"2020","unstructured":"Plante, J. A. et al. Spike mutation D614G alters SARS-CoV-2 fitness. Nature 592, 116\u2013121 (2020).","journal-title":"Nature"},{"key":"4266_CR10","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.cell.2020.11.020","volume":"184","author":"E Volz","year":"2021","unstructured":"Volz, E. et al. Evaluating the effects of SARS-CoV-2 spike mutation D614G on transmissibility and pathogenicity. Cell 184, 64\u201375 (2021).","journal-title":"Cell"},{"key":"4266_CR11","unstructured":"SARS-CoV-2 Variant Classifications and Definitions https:\/\/www.cdc.gov\/coronavirus\/2019-ncov\/variants\/variant-info.html (CDC, 2021)."},{"key":"4266_CR12","unstructured":"Tracking SARS-CoV-2 Variants https:\/\/www.who.int\/en\/activities\/tracking-SARS-CoV-2-variants\/ (WHO, 2021)."},{"key":"4266_CR13","unstructured":"3 June 2021 Risk Assessment for SARS-CoV-2 Variant: Delta (VOC-21APR-02, B.1.617.2)https:\/\/assets.publishing.service.gov.uk\/government\/uploads\/system\/uploads\/attachment_data\/file\/991135\/3_June_2021_Risk_assessment_for_SARS-CoV-2_variant_DELTA.pdf (Public Health England, 2021)."},{"key":"4266_CR14","doi-asserted-by":"publisher","first-page":"2461","DOI":"10.1016\/S0140-6736(21)01358-1","volume":"397","author":"A Sheikh","year":"2021","unstructured":"Sheikh, A. et al. SARS-CoV-2 Delta VOC in Scotland: demographics, risk of hospital admission, and vaccine effectiveness. Lancet 397, 2461\u20132462 (2021).","journal-title":"Lancet"},{"key":"4266_CR15","doi-asserted-by":"publisher","unstructured":"Twohig, K. A. et al. Hospital admission and emergency care attendance risk for SARS-CoV-2 Delta (B.1.617.2) compared with Alpha (B.1.1.7) variants of concern: a cohort study. Lancet Infect. Dis. https:\/\/doi.org\/10.1016\/S0140-6736(21)01358-1 (2021).","DOI":"10.1016\/S0140-6736(21)01358-1"},{"key":"4266_CR16","doi-asserted-by":"publisher","first-page":"11727","DOI":"10.1073\/pnas.2003138117","volume":"117","author":"J Shang","year":"2020","unstructured":"Shang, J. et al. Cell entry mechanisms of SARS-CoV-2. Proc. Natl Acad. Sci. USA 117, 11727\u201311734 (2020).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"4266_CR17","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1038\/s41579-021-00573-0","volume":"19","author":"WT Harvey","year":"2021","unstructured":"Harvey, W. T. et al. SARS-CoV-2 variants, spike mutations and immune escape. Nat. Rev. Microbiol. 19, 409\u2013424 (2021).","journal-title":"Nat. Rev. Microbiol."},{"key":"4266_CR18","doi-asserted-by":"publisher","first-page":"3086","DOI":"10.1016\/j.cell.2021.05.005","volume":"184","author":"D Corti","year":"2021","unstructured":"Corti, D., Purcell, L. A., Snell, G. & Veesler, D. Tackling COVID-19 with neutralizing monoclonal antibodies. Cell 184, 3086\u20133108 (2021).","journal-title":"Cell"},{"key":"4266_CR19","doi-asserted-by":"publisher","first-page":"2331","DOI":"10.1016\/S0140-6736(21)01290-3","volume":"397","author":"EC Wall","year":"2021","unstructured":"Wall, E. C. et al. Neutralising antibody activity against SARS-CoV-2 VOCs B.1.617.2 and B.1.351 by BNT162b2 vaccination. Lancet, 397, 2331\u20132333 (2021).","journal-title":"Lancet"},{"key":"4266_CR20","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1038\/s41586-021-03777-9","volume":"596","author":"D Planas","year":"2021","unstructured":"Planas, D. et al. Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization. Nature 596, 276\u2013280 (2021).","journal-title":"Nature"},{"key":"4266_CR21","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1097\/RTI.0000000000000524","volume":"35","author":"S Simpson","year":"2020","unstructured":"Simpson, S. et al. Radiological Society of North America expert consensus statement on reporting chest CT findings related to COVID-19. Endorsed by the Society of Thoracic Radiology, the American College of Radiology, and RSNA\u2014secondary publication. J. Thorac. Imaging 35, 219\u2013227 (2020).","journal-title":"J. Thorac. Imaging"},{"key":"4266_CR22","doi-asserted-by":"publisher","first-page":"899","DOI":"10.1038\/s41564-021-00908-w","volume":"6","author":"TP Peacock","year":"2021","unstructured":"Peacock, T. P. et al. The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets. Nat. Microbiol. 6, 899\u2013909 (2021).","journal-title":"Nat. Microbiol."},{"key":"4266_CR23","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1038\/s41586-021-03237-4","volume":"591","author":"BA Johnson","year":"2021","unstructured":"Johnson, B. A. et al. Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis. Nature 591, 293\u2013299 (2021).","journal-title":"Nature"},{"key":"4266_CR24","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-4-89","volume":"4","author":"J Sterjovski","year":"2007","unstructured":"Sterjovski, J. et al. Asn 362 in gp120 contributes to enhanced fusogenicity by CCR5-restricted HIV-1 envelope glycoprotein variants from patients with AIDS. Retrovirology 4, 89 (2007).","journal-title":"Retrovirology"},{"key":"4266_CR25","doi-asserted-by":"publisher","first-page":"3899","DOI":"10.1093\/emboj\/17.14.3899","volume":"17","author":"T Cathomen","year":"1998","unstructured":"Cathomen, T. et al. A matrix-less measles virus is infectious and elicits extensive cell fusion: consequences for propagation in the brain. EMBO J. 17, 3899\u20133908 (1998).","journal-title":"EMBO J."},{"key":"4266_CR26","doi-asserted-by":"publisher","first-page":"e2026027118","DOI":"10.1073\/pnas.2026027118","volume":"118","author":"S Ikegame","year":"2021","unstructured":"Ikegame, S. et al. Fitness selection of hyperfusogenic measles virus F proteins associated with neuropathogenic phenotypes. Proc. Natl Acad. Sci. USA 118, e2026027118 (2021).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"4266_CR27","doi-asserted-by":"publisher","first-page":"2648","DOI":"10.1128\/JVI.02632-12","volume":"87","author":"S Watanabe","year":"2013","unstructured":"Watanabe, S. et al. Mutant fusion proteins with enhanced fusion activity promote measles virus spread in human neuronal cells and brains of suckling hamsters. J. Virol. 87, 2648\u20132659 (2013).","journal-title":"J. Virol."},{"key":"4266_CR28","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-5-89","volume":"5","author":"F Rossi","year":"2008","unstructured":"Rossi, F. et al. The V1-V3 region of a brain-derived HIV-1 envelope glycoprotein determines macrophage tropism, low CD4 dependence, increased fusogenicity and altered sensitivity to entry inhibitors. Retrovirology 5, 89 (2008).","journal-title":"Retrovirology"},{"key":"4266_CR29","doi-asserted-by":"publisher","first-page":"7001","DOI":"10.1073\/pnas.2002589117","volume":"117","author":"S Matsuyama","year":"2020","unstructured":"Matsuyama, S. et al. Enhanced isolation of SARS-CoV-2 by TMPRSS2-expressing cells. Proc. Natl Acad. Sci. USA 117, 7001\u20137003 (2020).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"4266_CR30","doi-asserted-by":"crossref","unstructured":"Mlcochova, P. et al. SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion. Nature 599, 114\u2013119 (2021).","DOI":"10.1038\/s41586-021-03944-y"},{"key":"4266_CR31","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21118-2","volume":"12","author":"S Ozono","year":"2021","unstructured":"Ozono, S. et al. SARS-CoV-2 D614G spike mutation increases entry efficiency with enhanced ACE2-binding affinity. Nat. Commun. 12, 848 (2021).","journal-title":"Nat. Commun."},{"key":"4266_CR32","doi-asserted-by":"publisher","first-page":"109014","DOI":"10.1016\/j.celrep.2021.109014","volume":"35","author":"S Torii","year":"2021","unstructured":"Torii, S. et al. Establishment of a reverse genetics system for SARS-CoV-2 using circular polymerase extension reaction. Cell Rep. 35, 109014 (2021).","journal-title":"Cell Rep."},{"key":"4266_CR33","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1148\/radiol.2020200230","volume":"295","author":"M Chung","year":"2020","unstructured":"Chung, M. et al. CT imaging features of 2019 novel coronavirus (2019-nCoV). Radiology 295, 202\u2013207 (2020).","journal-title":"Radiology"},{"key":"4266_CR34","doi-asserted-by":"publisher","first-page":"772","DOI":"10.1093\/molbev\/mst010","volume":"30","author":"K Katoh","year":"2013","unstructured":"Katoh, K. & Standley, D. M. MAFFT multiple sequence alignment software version 7: improvements in performance and usability. Mol. Biol. Evol. 30, 772\u2013780 (2013).","journal-title":"Mol. Biol. Evol."},{"key":"4266_CR35","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1093\/molbev\/msaa015","volume":"37","author":"BQ Minh","year":"2020","unstructured":"Minh, B. Q. et al. IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic era. Mol. Biol. Evol. 37, 1530\u20131534 (2020).","journal-title":"Mol. Biol. Evol."},{"key":"4266_CR36","first-page":"493","volume":"27","author":"LJ Reed","year":"1938","unstructured":"Reed, L. J. & Muench, H. A simple method of estimating fifty percent endpoints. Am. J. Hygiene 27, 493\u2013497 (1938).","journal-title":"Am. J. Hygiene"},{"key":"4266_CR37","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.1016\/j.chom.2021.06.006","volume":"29","author":"C Motozono","year":"2021","unstructured":"Motozono, C. et al. SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity. Cell Host Microbe 29, 1124\u20131136 (2021).","journal-title":"Cell Host Microbe"},{"key":"4266_CR38","doi-asserted-by":"publisher","first-page":"230","DOI":"10.1186\/s12864-020-6635-8","volume":"21","author":"T Rausch","year":"2020","unstructured":"Rausch, T., Fritz, M. H., Untergasser, A. & Benes, V. Tracy: basecalling, alignment, assembly and deconvolution of sanger chromatogram trace files. BMC Genom. 21, 230 (2020).","journal-title":"BMC Genom."},{"key":"4266_CR39","doi-asserted-by":"publisher","first-page":"i884","DOI":"10.1093\/bioinformatics\/bty560","volume":"34","author":"S Chen","year":"2018","unstructured":"Chen, S., Zhou, Y., Chen, Y. & Gu, J. fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics 34, i884\u2013i890 (2018).","journal-title":"Bioinformatics"},{"key":"4266_CR40","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1093\/bioinformatics\/btp698","volume":"26","author":"H Li","year":"2010","unstructured":"Li, H. & Durbin, R. Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 26, 589\u2013595 (2010).","journal-title":"Bioinformatics"},{"key":"4266_CR41","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giab008","volume":"10","author":"P Danecek","year":"2021","unstructured":"Danecek, P. et al. Twelve years of SAMtools and BCFtools. Gigascience 10, giab008 (2021).","journal-title":"Gigascience"},{"key":"4266_CR42","doi-asserted-by":"publisher","first-page":"80","DOI":"10.4161\/fly.19695","volume":"6","author":"P Cingolani","year":"2012","unstructured":"Cingolani, P. et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly 6, 80\u201392 (2012).","journal-title":"Fly"},{"key":"4266_CR43","doi-asserted-by":"publisher","first-page":"e00658","DOI":"10.1128\/mSphere.00658-20","volume":"5","author":"C Shema Mugisha","year":"2020","unstructured":"Shema Mugisha, C. et al. A simplified quantitative real-time PCR assay for monitoring SARS-CoV-2 growth in cell culture. mSphere 5, e00658-20 (2020).","journal-title":"mSphere"},{"key":"4266_CR44","doi-asserted-by":"publisher","unstructured":"Kimura, I. et al. SARS-CoV-2 Lambda variant exhibits higher infectivity and immune resistance. Cell Rep. https:\/\/doi.org\/10.1016\/j.celrep.2021.110218 (2021).","DOI":"10.1016\/j.celrep.2021.110218"},{"key":"4266_CR45","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/0378-1119(91)90434-D","volume":"108","author":"H Niwa","year":"1991","unstructured":"Niwa, H., Yamamura, K. & Miyazaki, J. Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene 108, 193\u2013199 (1991).","journal-title":"Gene"},{"key":"4266_CR46","doi-asserted-by":"publisher","first-page":"13023","DOI":"10.1074\/jbc.RA120.013887","volume":"295","author":"S Ozono","year":"2020","unstructured":"Ozono, S., Zhang, Y., Tobiume, M., Kishigami, S. & Tokunaga, K. Super-rapid quantitation of the production of HIV-1 harboring a luminescent peptide tag. J. Biol. Chem. 295, 13023\u201313030 (2020).","journal-title":"J. Biol. Chem."},{"key":"4266_CR47","doi-asserted-by":"publisher","first-page":"1140","DOI":"10.1099\/jgv.0.001276","volume":"100","author":"T Ikeda","year":"2019","unstructured":"Ikeda, T. et al. HIV-1 restriction by endogenous APOBEC3G in the myeloid cell line THP-1. J. Gen. Virol. 100, 1140\u20131152 (2019).","journal-title":"J. Gen. Virol."},{"key":"4266_CR48","doi-asserted-by":"publisher","first-page":"e1007010","DOI":"10.1371\/journal.ppat.1007010","volume":"14","author":"T Ikeda","year":"2018","unstructured":"Ikeda, T. et al. HIV-1 adaptation studies reveal a novel Env-mediated homeostasis mechanism for evading lethal hypermutation by APOBEC3G. PLoS Pathog. 14, e1007010 (2018).","journal-title":"PLoS Pathog."},{"key":"4266_CR49","doi-asserted-by":"publisher","first-page":"e00986","DOI":"10.1128\/JVI.00986-19","volume":"93","author":"T Sultana","year":"2019","unstructured":"Sultana, T. et al. Multiple pathways to avoid beta interferon sensitivity of HIV-1 by mutations in capsid. J. Virol. 93, e00986-19 (2019).","journal-title":"J. Virol."},{"key":"4266_CR50","doi-asserted-by":"publisher","first-page":"26.9.1","DOI":"10.1002\/0471143030.cb2609s50","volume":"50,","author":"N Kondo","year":"2011","unstructured":"Kondo, N., Miyauchi, K. & Matsuda, Z. Monitoring viral-mediated membrane fusion using fluorescent reporter methods. Curr. Protoc. Cell Biol. 50, 26.9.1\u201326.9.9 (2011).","journal-title":"Curr. Protoc. Cell Biol."}],"container-title":["Nature"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41586-021-04266-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-021-04266-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41586-021-04266-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T02:17:33Z","timestamp":1675909053000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41586-021-04266-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,25]]},"references-count":50,"journal-issue":{"issue":"7896","published-print":{"date-parts":[[2022,2,10]]}},"alternative-id":["4266"],"URL":"https:\/\/doi.org\/10.1038\/s41586-021-04266-9","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.06.17.448820","asserted-by":"object"}]},"ISSN":["0028-0836","1476-4687"],"issn-type":[{"value":"0028-0836","type":"print"},{"value":"1476-4687","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,25]]},"assertion":[{"value":"22 July 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 November 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 November 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}