SARS-CoV-2 D614G Variant Exhibits Efficient Replication ex vivo and Transmission in vivo
By Yixuan J. Hou, S. Chiba, P. Halfmann, C. Ehre, M. Kuroda, K. Dinnon, S. Leist, A. Schäfer, N. Nakajima, Kenta Takahashi and 16 more. Science, 2020
837 citations recorded by the source corpus.
Changing with the times Pandemic spread of a virus in naïe populations can select for mutations that alter pathogenesis, virulence, and/or transmissibility. The ancestral form of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that emerged from China has now been largely replaced by strains containing the mutation D614G (Asp614-to-Gly) in the viral spike protein. Hou et al. compared the characteristics of the new variant against the ancestral form in a series of experiments in human cells and animal models. The variant is better at infecting upper-airway epithelial cells and replicates in greater numbers than the ancestral virus. Evidence indicates modest, if any, significant changes to virulence in animal models. Therefore, the virus appears to have evolved for greater transmissibility in humans rather than for greater pathogenicity. The mutation renders the new virus variant more susceptible to neutralizing antisera without altering the efficacy of vaccine candidates currently under development. Science, this issue p. 1464 The current dominant structural variant of SARS-CoV-2 appears to have evolved from the ancestral form and enhances transmissibility. The spike aspartic acid–614 to glycine (D614G) substitution is prevalent in global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strains, but its effects on viral pathogenesis and transmissibility remain unclear. We engineered a SARS-CoV-2 variant containing this substitution. The variant exhibits more efficient infection, replication, and competitive fitness in primary human airway epithelial cells but maintains similar morphology and in vitro neutralization properties, compared with the ancestral wild-type virus. Infection of human angiotensin-converting enzyme 2 (ACE2) transgenic mice and Syrian hamsters with both viruses resulted in similar viral titers in respiratory tissues and pulmonary disease. However, the D614G variant transmits significantly faster and displayed increased competitive fitness than the wild-type virus in hamsters. These data show that the D614G substitution enhances SARS-CoV-2 infectivity, competitive fitness, and transmission in primary human cells and animal models.
Subfields: Infectious Diseases
View Paper: https://www.semanticscholar.org/paper/cf53da1c6822745338081377c05aaa90cebdfafa
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In Infectious Diseases
Citations in the corpus
- SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma (2021, neutral): “Amongst previous lineages, D614G was shown to have faster growth in vitr o, enhanced transmission in small animals, and has subsequently become globally dominant 28-30 .”
- COVID-19 neutralizing antibodies predict disease severity and survival (2020, neutral): “Recent studies have demonstrated that infection with live SARS-CoV-2 harboring the D614G spike variant yielded higher virus titers in respiratory cultures and increased transmissibility in hamstermodels (Plante et al., 2020; Zhou et al., 2020a; Hou et al., 2020).”
- Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity (2021, neutral): “convalescent individuals showed effective cross-neutralization of both wild type and D614G variants (Garcia-Beltran et al., 2021; Legros et al., 2021; Hou et al., 2020).”
- Neutralizing and protective human monoclonal antibodies recognizing the N-terminal domain of the SARS-CoV-2 spike protein (2021, background): “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).”
- The Omicron variant is highly resistant against antibody-mediated neutralization: Implications for control of the COVID-19 pandemic (2021, neutral): “…mutations in spike increase transmissibility and which mechanisms 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., 2021; Plante et al., 2021; Zhou et al., 2021).”
- Nanobody cocktails potently neutralize SARS-CoV-2 D614G N501Y variant and protect mice (2021, neutral): “In particular, all three variants share one specific mutation called D614G, which replaced the initial SARS-CoV-2 strain to become the dominant form of the virus circulating globally and is thought to promote transmission of the virus but with no impact on pathogenesis (16).”