دورية أكاديمية

The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types.

التفاصيل البيبلوغرافية
العنوان: The Spike D614G mutation increases SARS-CoV-2 infection of multiple human cell types.
المؤلفون: Daniloski Z; New York Genome Center, New York, United States.; Department of Biology, New York University, New York, United States., Jordan TX; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, United States., Ilmain JK; Department of Cell Biology and Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, United States., Guo X; New York Genome Center, New York, United States.; Department of Biology, New York University, New York, United States., Bhabha G; Department of Cell Biology and Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, United States., tenOever BR; Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, United States., Sanjana NE; New York Genome Center, New York, United States.; Department of Biology, New York University, New York, United States.
المصدر: ELife [Elife] 2021 Feb 11; Vol. 10. Date of Electronic Publication: 2021 Feb 11.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: eLife Sciences Publications, Ltd Country of Publication: England NLM ID: 101579614 Publication Model: Electronic Cited Medium: Internet ISSN: 2050-084X (Electronic) Linking ISSN: 2050084X NLM ISO Abbreviation: Elife Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Cambridge, UK : eLife Sciences Publications, Ltd., 2012-
مواضيع طبية MeSH: Mutation, Missense*, COVID-19/*virology , SARS-CoV-2/*metabolism , Spike Glycoprotein, Coronavirus/*genetics, Angiotensin-Converting Enzyme 2/genetics ; Angiotensin-Converting Enzyme 2/metabolism ; COVID-19/genetics ; COVID-19/metabolism ; Humans ; SARS-CoV-2/genetics ; Spike Glycoprotein, Coronavirus/metabolism
مستخلص: A novel variant of the SARS-CoV-2 virus carrying a point mutation in the Spike protein (D614G) has recently emerged and rapidly surpassed others in prevalence. This mutation is in linkage disequilibrium with an ORF1b protein variant (P314L), making it difficult to discern the functional significance of the Spike D614G mutation from population genetics alone. Here, we perform site-directed mutagenesis on wild-type human-codon-optimized Spike to introduce the D614G variant. Using multiple human cell lines, including human lung epithelial cells, we found that the lentiviral particles pseudotyped with Spike D614G are more effective at transducing cells than ones pseudotyped with wild-type Spike. The increased transduction with Spike D614G ranged from 1.3- to 2.4-fold in Caco-2 and Calu-3 cells expressing endogenous ACE2 and from 1.5- to 7.7-fold in A549 ACE2 and Huh7.5 ACE2 overexpressing ACE2. Furthermore, trans -complementation of SARS-CoV-2 virus with Spike D614G showed an increased infectivity in human cells. Although there is minimal difference in ACE2 receptor binding between the D614 and G614 Spike variants, the G614 variant is more resistant to proteolytic cleavage, suggesting a possible mechanism for the increased transduction.
Competing Interests: ZD, TJ, JI, XG, GB, Bt No competing interests declared, NS N.E.S. is an advisor to Vertex.
(© 2021, Daniloski et al.)
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معلومات مُعتمدة: R01 AI123155 United States AI NIAID NIH HHS; R01 CA218668 United States CA NCI NIH HHS; 20POST35220040 American Heart Association; DP2 HG010099 United States HG NHGRI NIH HHS; R00 HG008171 United States HG NHGRI NIH HHS; R01AI147131 National Institute of Allergy and Infectious Diseases; R01 AI147131 United States AI NIAID NIH HHS; R00HG008171 United States GF NIH HHS; HR0011-20-2-0040 Defense Advanced Research Projects Agency; R01AI123155 National Institute of Allergy and Infectious Diseases; DP2HG010099 United States HG NHGRI NIH HHS; R01CA218668 United States CA NCI NIH HHS; PEW-00033055 Pew Charitable Trusts; D18AP00053 Defense Advanced Research Projects Agency; SSP-2018-2737 Searle Scholars Program
فهرسة مساهمة: Keywords: COVID-19; D614G; SARS-CoV-2; Spike; coronavirus; epidemiology; global health; human; infectious disease; microbiology; virus
المشرفين على المادة: 0 (Spike Glycoprotein, Coronavirus)
0 (spike protein, SARS-CoV-2)
EC 3.4.17.23 (ACE2 protein, human)
EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
تواريخ الأحداث: Date Created: 20210211 Date Completed: 20210225 Latest Revision: 20210225
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC7891930
DOI: 10.7554/eLife.65365
PMID: 33570490
قاعدة البيانات: MEDLINE
الوصف
تدمد:2050-084X
DOI:10.7554/eLife.65365