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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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“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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Self-citationSARS-CoV-2 Reverse Genetics Reveals a Variable Infection Gradient in the Respiratory Tract
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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
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Self-citationEvaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity
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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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