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Spike mutation D614G alters SARS-CoV-2 fitness
Open accessPublished version of a preprint
Abstract
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein substitution D614G became dominant during the coronavirus disease 2019 (COVID-19) pandemic 1,2. However, the effect of this variant on viral spread and vaccine efficacy remains to be defined. Here we engineered the spike D614G substitution in the USA-WA1/2020 SARS-CoV-2 strain, and found that it enhances viral replication in human lung epithelial cells and primary human airway tissues by increasing the infectivity and stability of virions. Hamsters infected with SARS-CoV-2 expressing spike(D614G) (G614 virus) produced higher infectious titres in nasal washes and the trachea, but not in the lungs, supporting clinical evidence showing that the mutation enhances viral loads in the upper respiratory tract of COVID-19 patients and may increase transmission. Sera from hamsters infected with D614 virus exhibit modestly higher neutralization titres against G614 virus than against D614 virus, suggesting that the mutation is unlikely to reduce the ability of vaccines in clinical trials to protect against COVID-19, and that therapeutic antibodies should be tested against the circulating G614 virus. Together with clinical findings, our work underscores the importance of this variant in viral spread and its implications for vaccine efficacy and antibody therapy.
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In the citing paper
“Jessica A et al. [26] studied replication kinetics of the D614G variant in human lung epithelial cell line Calu-3 and found 2.4-fold more infectious virus 36 hpi, indicating enhanced viral replication.”
From Waves and variants of SARS-CoV-2: understanding the causes and effect of the COVID-19 catastrophe (2022) · cites this paper as [26]
In the citing paper
“One of the first identified variants includes the D614G mutation in the gene encoding the spike (S) protein, which enhances viral infectivity and shifts S protein conformation toward an angiotensin-converting enzyme 2 (ACE2)-binding fusion-competent state, without significantly modifying sensitivity to antibody neutralization 1,[6][7][8] .”
From Sensitivity of infectious SARS-CoV-2 B.1.1.7 and B.1.351 variants to neutralizing antibodies (2021) · cites this paper as [7]
In the citing paper
“The D614G mutation is dominant in circulating strains around the world 7,8 .”
From Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera (2021) · cites this paper as [7]
In the citing paper
“The emergence of the common mutation N501Y from different geographical regions, as well as the previously emerged globally dominant D614G mutation, suggest that these mutations might improve viral fitness”
From Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera (2021) · cites this paper as [7]
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Cites
A pneumonia outbreak associated with a new coronavirus of probable bat origin
Zhou, P., Yang, X.-L., Wang, X.-G., Hu, B., Zhang, L., Zhang, W., Si, H.-R., Zhu, Y., Li, B., Huang, C.-L., et al. (2020) · Nature · doi:10.1038/s41586-020-2012-7 · Cited by 21,969
Hoffmann, M., Kleine-Weber, H., Schroeder, S., Krüger, N., Herrler, T., Erichsen, S., Schiergens, T. S., Herrler, G., Wu, N.-H., Nitsche, A., et al. (2020) · Cell · doi:10.1016/j.cell.2020.02.052 · Cited by 20,286
Virological assessment of hospitalized patients with COVID-2019
Wölfel, R., Corman, V. M., Guggemos, W., Seilmaier, M., Zange, S., Müller, M. A., Niemeyer, D., Jones, T. C., Vollmar, P., Rothe, C., et al. (2020) · Nature · doi:10.1038/s41586-020-2196-x · Cited by 6,661
Korber, B., Fischer, W. M., Gnanakaran, S., Yoon, H., Theiler, J., Abfalterer, W., Hengartner, N., Giorgi, E. E., Bhattacharya, T., Foley, B., et al. (2020) · Cell · doi:10.1016/j.cell.2020.06.043 · Cited by 4,281
An mRNA Vaccine against SARS-CoV-2 — Preliminary Report
Jackson, L. A., Anderson, E. J., Rouphael, N. G., Roberts, P. C., Makhene, M., Coler, R. N., McCullough, M. P., Chappell, J. D., Denison, M. R., Stevens, L. J., et al. (2020) · New England Journal of Medicine · doi:10.1056/nejmoa2022483 · Cited by 3,237
The New Statistics: Why and How
Cumming, G. (2014) · Psychological Science · doi:10.1177/0956797613504966 · Cited by 3,200
HCA Lung Biological Network, Sungnak, W., Huang, N., Bécavin, C., Berg, M., Queen, R., Litvinukova, M., Talavera-López, C., Maatz, H., Reichart, D., et al. (2020) · Nature Medicine · doi:10.1038/s41591-020-0868-6 · Cited by 2,501
Hoffmann, M., Kleine-Weber, H., & Pöhlmann, S. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.04.022 · Cited by 1,852
Mulligan, M. J., Lyke, K. E., Kitchin, N., Absalon, J., Gurtman, A., Lockhart, S., Neuzil, K., Raabe, V., Bailey, R., Swanson, K. A., et al. (2020) · doi:10.1101/2020.06.30.20142570 · Cited by 1,569
Self-citationSARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract
Hou, Y. J., Okuda, K., Edwards, C. E., Martinez, D. R., Asakura, T., Dinnon, K. H., Kato, T., Lee, R. E., Yount, B. L., Mascenik, T. M., et al. (2020) · Cell · doi:10.1016/j.cell.2020.05.042 · Cited by 1,488
SARS-CoV-2 spike-protein D614G mutation increases virion spike density and infectivity
Zhang, L., Jackson, C. B., Mou, H., Ojha, A., Peng, H., Quinlan, B. D., Rangarajan, E. S., Pan, A., Vanderheiden, A., Suthar, M. S., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19808-4 · Cited by 1,387
Sungnak, W., Huang, N., Bécavin, C., & Berg, M. (2020) · PubMed · Cited by 1,196
Chan, J. F., Zhang, J., Yuan, S., Poon, V. K., Chan, C. C., Lee, A. C.-Y., Chan, W.-M., Fan, Z., Tsoi, H.-W., Wen, L., et al. (2020) · Clinical Infectious Diseases · doi:10.1093/cid/ciaa325 · Cited by 1,048
Structural and Functional Analysis of the D614G SARS-CoV-2 Spike Protein Variant
Yurkovetskiy, L., Wang, X., Pascal, K. E., Tomkins-Tinch, C., Nyalile, T. P., Wang, Y., Baum, A., Diehl, W. E., Dauphin, A., Carbone, C., et al. (2020) · Cell · doi:10.1016/j.cell.2020.09.032 · Cited by 1,025
SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo
Hou, Y. J., Chiba, S., Halfmann, P., Ehre, C., Kuroda, M., Dinnon, K. H., Leist, S. R., Schäfer, A., Nakajima, N., Takahashi, K., et al. (2020) · Science · doi:10.1126/science.abe8499 · Cited by 900
Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis
Johnson, B. A., Xie, X., Bailey, A. L., Kalveram, B., Lokugamage, K. G., Muruato, A., Zou, J., Zhang, X., Juelich, T., Smith, J. K., et al. (2021) · Nature · doi:10.1038/s41586-021-03237-4 · Cited by 694
Self-citationCross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human
Song, H., Tu, C., Zhang, G., Wang, S., Zheng, K. C., Lei, L., Chen, Q., Gao, Y., Zhou, H., Xiang, H., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409608102 · Cited by 693
Self-citationAn Infectious cDNA Clone of SARS-CoV-2
Xie, X., Muruato, A., Lokugamage, K. G., Narayanan, K., Zhang, X., Zou, J., Liu, J., Schindewolf, C., Bopp, N. E., Aguilar, P. V., et al. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.04.004 · Cited by 647
Self-citationThe D614G mutation in the SARS-CoV-2 spike protein reduces S1 shedding and increases infectivityPreprint
Zhang, L., Jackson, C. B., Mou, H., et al. (2020) · bioRxiv · doi:10.1101/2020.06.12.148726 · Cited by 576
Severe Acute Respiratory Syndrome Coronavirus 2 from Patient with Coronavirus Disease, United States
Harcourt, J. L., Tamin, A., Lu, X., Kamili, S., Sakthivel, S. K., Murray, J., Queen, K. J., Tao, Y., Paden, C. R., Zhang, J., et al. (2020) · Emerging infectious diseases · doi:10.3201/eid2606.200516 · Cited by 534
Self-citationBöhmer, M. M., Buchholz, U., Corman, V. M., Hoch, M., Katz, K., Marosevic, D., Böhm, S., Woudenberg, T., Ackermann, N., Konrad, R., et al. (2020) · The Lancet Infectious Diseases · doi:10.1016/s1473-3099(20)30314-5 · Cited by 462
Smith, E. C., Blanc, H., Vignuzzi, M., & Denison, M. R. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003565 · Cited by 428
Coast-to-Coast Spread of SARS-CoV-2 during the Early Epidemic in the United States
Fauver, J. R., Petrone, M. E., Hodcroft, E. B., Shioda, K., Ehrlich, H. Y., Watts, A., Vogels, C. B. F., Brito, A. F., Alpert, T., Muyombwe, A., et al. (2020) · Cell · doi:10.1016/j.cell.2020.04.021 · Cited by 319
A high-throughput neutralizing antibody assay for COVID-19 diagnosis and vaccine evaluation
Muruato, A. E., Fontes-Garfias, C. R., Ren, P., Garcia-Blanco, M. A., Menachery, V. D., Xie, X., & Shi, P.-Y. (2020) · Nature Communications · doi:10.1038/s41467-020-17892-0 · Cited by 319
Self-citationThe Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types
Daniloski, Z., Jordan, T. X., Ilmain, J. K., Guo, X., Bhabha, G., tenOever, B. R., & Sanjana, N. E. (2021) · eLife · doi:10.7554/elife.65365 · Cited by 233
Furin Cleavage Site Is Key to SARS-CoV-2 PathogenesisPreprint
Johnson, B. A., Xie, X., Kalveram, B., Lokugamage, K. G., Muruato, A. E., Zou, J., Zhang, X., Juelich, T. L., Smith, J. K., Zhang, L., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.08.26.268854 · Cited by 186
Self-citationInfluenza A viruses are transmitted via the air from the nasal respiratory epithelium of ferrets
Richard, M., van den Brand, J. M. A., Bestebroer, T. M., Lexmond, P., de Meulder, D., Fouchier, R. A. M., Lowen, A. C., & Herfst, S. (2020) · Nature Communications · doi:10.1038/s41467-020-14626-0 · Cited by 175
The four horsemen of a viral Apocalypse: The pathogenesis of SARS-CoV-2 infection (COVID-19)
Domingo, P., Mur, I., Pomar, V., Corominas, H., Casademont, J., & Benito, N. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.102887 · Cited by 174
Coffey, L. L., & Vignuzzi, M. (2010) · Journal of Virology · doi:10.1128/jvi.01918-10 · Cited by 166
A Comparison of Methods to Measure Fitness in Escherichia coli
Wiser, M. J., & Lenski, R. E. (2015) · PLOS ONE · doi:10.1371/journal.pone.0126210 · Cited by 162
Grubaugh, N. D., Weger‐Lucarelli, J., Murrieta, R. A., Fauver, J. R., Garcia-Luna, S., Prasad, A. N., Black, W. C., & Ebel, G. D. (2016) · Cell Host & Microbe · doi:10.1016/j.chom.2016.03.002 · Cited by 146
The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell typesPreprint
Daniloski, Z., Jordan, T. X., Ilmain, J. K., Guo, X., Bhabha, G., tenOever, B. R., & Sanjana, N. E. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.06.14.151357 · Cited by 138
A Unique Clade of SARS-CoV-2 Viruses is Associated with Lower Viral Loads in Patient Upper Airways
Lorenzo-Redondo, R., Nam, H. H., Roberts, S. C., Simons, L. M., Jennings, L. J., Qi, C., Achenbach, C. J., Hauser, A. R., Ison, M. G., Hultquist, J. F., et al. (2020) · doi:10.1101/2020.05.19.20107144 · Cited by 111
A clade of SARS-CoV-2 viruses associated with lower viral loads in patient upper airways
Lorenzo-Redondo, R., Nam, H. H., Roberts, S. C., Simons, L. M., Jennings, L. J., Qi, C., Achenbach, C. J., Hauser, A. R., Ison, M. G., Hultquist, J. F., et al. (2020) · EBioMedicine · doi:10.1016/j.ebiom.2020.103112 · Cited by 110
Inferring relative proportions of DNA variants from sequencing electropherograms
Carr, I., Robinson, J. I., Dimitriou, R. I., Markham, A. F., Morgan, A. W., & Bonthron, D. T. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp583 · Cited by 106
Phenotypic Responses of Differentiated Asthmatic Human Airway Epithelial Cultures to Rhinovirus
Bai, J., Smock, S. L., Jackson, G. R., MacIsaac, K. D., Huang, Y., Mankus, C., Oldach, J., Roberts, B. S., Ma, Y.-L., Klappenbach, J. A., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0118286 · Cited by 71
Prevalidation of an Acute Inhalation Toxicity Test Using the EpiAirway In Vitro Human Airway Model
Jackson, G. R., Maione, A. G., Klausner, M., & Hayden, P. J. (2018) · Applied In Vitro Toxicology · doi:10.1089/aivt.2018.0004 · Cited by 71
Bergren, N. A., Haller, S. L., Rossi, S. L., Seymour, R. L., Huang, J., Miller, A. L., Bowen, R. A., Hartman, D. A., Brault, A. C., & Weaver, S. C. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1008102 · Cited by 53
Self-citationSARS-CoV-2 D614G Variant Exhibits Enhanced Replication ex vivo and Earlier Transmission in vivoPreprint
Hou, Y. J., Chiba, S., Halfmann, P., et al. (2020) · bioRxiv · doi:10.1101/2020.09.28.317685 · Cited by 50
A high-throughput neutralizing antibody assay for COVID-19 diagnosis and vaccine evaluationPreprint
Muruato, A. E., Fontes-Garfias, C. R., Ren, P., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.05.21.109546 · Cited by 49
Self-citationcatseyes: Create Catseye Plots Illustrating the Normal Distribution of the Means
Andersen, C. (2019) · doi:10.32614/cran.package.catseyes · Cited by 17
Clinical anatomy of the European hamster : Cricetus cricetus, L
Reznik, G. K., Schuller, H. M., Mohr, U., Dodson, P., Walter, P. C., & Levine, R. B. (1978) · U.S. Government Printing Office eBooks · doi:10.5962/bhl.title.105391 · Cited by 13
Research works printed but not linked: 1
- Mulligan, M. J. et al. Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults. Nature 586, 589–593 (2020). · DOI · Paper page
Cited by
Sorted by citations
Detection of a SARS-CoV-2 variant of concern in South Africa
Tegally, H., Wilkinson, E., Giovanetti, M., Iranzadeh, A., Fonseca, V., Giandhari, J., Doolabh, D., Pillay, S., San, E. J., Msomi, N., et al. (2021) · Nature · doi:10.1038/s41586-021-03402-9 · Cited by 2,510
Self-citationMultiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity
Garcia-Beltran, W. F., Lam, E. C., St. Denis, K., Nitido, A. D., Garcia, Z. H., Hauser, B. M., Feldman, J., Pavlovic, M. N., Gregory, D. J., Poznansky, M. C., et al. (2021) · Cell · doi:10.1016/j.cell.2021.03.013 · Cited by 1,353
Tegally, H., Wilkinson, E., Giovanetti, M., Iranzadeh, A., Fonseca, V., Giandhari, J., Doolabh, D., Pillay, S., San, E. J., Msomi, N., et al. (2020) · doi:10.1101/2020.12.21.20248640 · Cited by 2,535
Self-citationEvaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity
Volz, E., Hill, V., McCrone, J. T., Price, A., Jorgensen, D., O’Toole, Á., Southgate, J., Johnson, R., Jackson, B., Nascimento, F. F., et al. (2021) · Cell · doi:10.1016/j.cell.2020.11.020 · Cited by 1,006
Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift
Cameroni, E., Bowen, J. E., Rosen, L. E., Saliba, C., Zepeda, S. K., Culap, K., Pinto, D., VanBlargan, L. A., Marco, A. D., di Iulio, J., et al. (2021) · Nature · doi:10.1038/s41586-021-04386-2 · Cited by 1,070
Metadata
- Authors
- Plante, J. A., Liu, Y., Liu, J., Xia, H., Johnson, B. A., Lokugamage, K. G., Zhang, X., Muruato, A. E., Zou, J., Fontes-Garfias, C. R., Mirchandani, D., Scharton, D., Bilello, J. P., Ku, Z., An, Z., Kalveram, B., Freiberg, A. N., Menachery, V. D., Xie, X., Plante, K. S., Weaver, S. C., & Shi, P.-Y.
- Affiliations
- The University of Texas Medical Branch at Galveston (US)
- Gilead Sciences (United States) (US)
- Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases (US)
- Corresponding author
- Xie, Xuping
- Plante, Kenneth S.
- Weaver, Scott C.
- Shi, Pei-Yong
- ORCID
- Venue
- Nature
- Published
- 2020-10-26
- Volume
- 592
- Issue
- 7852
- Pages
- 116-121
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC8158177
- OpenAlex
- W3093768302
- Cited by
- 1,558
- References
- 37
- Citations by year
- 2026: 37 · 2025: 73 · 2024: 120 · 2023: 174 · 2022: 427 · 2021: 670 · 2020: 55
- FWCI
- 43.60
- Type
- journal article
- Language
- en
- Update notices
- correction (2021-06-15)
- Open access
- bronze
- doi.org
- Locations
- Nature (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Amon G. Carter Foundation
- John S. Dunn Foundation (AI145617)
- University of Texas System
- Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation (AI134907)
- National Institutes of Health (AG049042, TL1TR001440, AI145617, AI142759, UL1TR001439)
- National Institute on Aging (AI142759, AG049042, R00AG049092)
- National Institute of Allergy and Infectious Diseases (R43AI145617, AI142759, R24AI120942, R01AI134907, R21AI145400, U01AI151801, U19AI142759, R01AI153602, AI153602, AG049042, AI134907, AI145617, UC7AI094660)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- SARS-CoV-2, viral fitness, viral replication, upper respiratory tract infection, virus transmission, neutralizing antibodies, vaccine efficacy, hamster model, lung epithelial cells, therapeutic antibodies
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