Spike mutation D614G alters SARS-CoV-2 fitness

By Jessica A. Plante, Yang Liu, Jianying Liu, Hongjie Xia, Bryan A. Johnson, K. Lokugamage, Xianwen Zhang, Antonio E. Muruato, Jing Zou, Camila R. Fontes-Garfias and 12 more. Nature, 2020

1,228 citations recorded by the source corpus.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein substitution D614G became dominant during the coronavirus disease 2019 (COVID-19) pandemic1,2. 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. The SARS-CoV-2 variant expressing spike(D641G) shows increased infectivity in human lung epithelial cells and in hamster and primary human upper airway tissues, but is more susceptible to neutralization by antibodies raised against SARS-CoV-2.

Subfields: Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/c1e122a7ce26712c8d0c25c83564b6e3254a2526

Citations in the corpus

• Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein (2021, neutral): “Since the start of the outbreak, circulating SARS-CoV-2 field strains have acquired genetic changes that facilitate transmission (Avanzato et al., 2020; Choi et al., 2020; Hou et al., 2020; Kemp et al., 2020; McCarthy et al., 2020; Plante et al., 2020; Rambaut et al., 2020; Tegally et al., 2020).”
• Circulating SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity (2021, neutral): “While several studies demonstrated that this strain is more infectious (Korber et al. 2020; Yurkovetskiy et al. 2020a, [b] 2020; Plante et al. 2020; Zhou et al. 2020; Hou et al. 2020), we and others found that sera from convalescent individuals showed effective cross-neutralization of both wildtype…”
• The Omicron variant is highly resistant against antibody-mediated neutralization: Implications for control of the COVID-19 pandemic (2021, neutral): “In contrast, it is less well understood which mutations in the spike increase transmissibility andwhichmechanisms are responsible, although it is well established that mutation D614G increases viral transmission and promotes ACE2 engagement (Hou et al., 2020; Korber et al., 2020; Mansbach et al., 20”
• Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice (2021, neutral): “Genomic sequencing shows that SARS-CoV-2 carrying G614 has replaced D614 as the predominant circulating variant and increases the infectivity of the virus (48, 49).”
• Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity (2021, neutral): “While several studies demonstrated that this strain is more infectious (Korber et al., 2020; Yurkovetskiy et al., 2020a, 2020b; Plante et al., 2020; Zhou et al., 2020; Hou et al., 2020), we and others found that sera from”
• SARS-CoV-2 variants B.1.351 and P.1 escape from neutralizing antibodies (2021, neutral): “The only exception was a D614G change in the viral S protein that became dominant early in the pandemic and that has been associated with increased transmissibility (Korber et al., 2020; Plante et al., 2020; Volz et al., 2021).”