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DOI10.1126/science.abe8499
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.; Lee R.E.; Mascenik T.M.; Graham R.; Edwards C.E.; Tse L.V.; Okuda K.; Markmann A.J.; Bartelt L.; Silva A.D.; Margolis D.M.; Boucher R.C.; Randell S.H.; Suzuki T.; Gralinski L.E.; Kawaoka Y.; Baric R.S.
发表日期2020
ISSN0036-8075
起始页码1464
结束页码1468
卷号370期号:6523
英文摘要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. © 2020 American Association for the Advancement of Science. All rights reserved.
英文关键词angiotensin converting enzyme 2; asparagine; glycine; bioengineering; disease transmission; pathogenicity; rodent; severe acute respiratory syndrome; virus; airway epithelium cell; Article; biological model; cell structure; comparative study; coronavirus disease 2019; ex vivo study; human; in vitro study; in vivo study; lung disease; lung parenchyma; nonhuman; pathogenesis; priority journal; Severe acute respiratory syndrome coronavirus 2; Severe acute respiratory syndrome coronavirus 2 D614G; virus load; virus neutralization; virus replication; virus strain; virus transmission; amino acid substitution; animal; genetics; hamster; Mesocricetus; mouse; pathogenicity; reproductive fitness; respiratory mucosa; transgenic mouse; virology; virulence; virus replication; Cricetinae; Mesocricetus auratus; Mus musculus; SARS coronavirus; Amino Acid Substitution; Angiotensin-Converting Enzyme 2; Animals; Asparagine; COVID-19; Cricetinae; Genetic Fitness; Glycine; Humans; Mesocricetus; Mice; Mice, Transgenic; Respiratory Mucosa; SARS-CoV-2; Virulence; Virus Replication
语种英语
来源期刊Science
文献类型期刊论文
条目标识符http://gcip.llas.ac.cn/handle/2XKMVOVA/244062
作者单位Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Influenza Research Institute, School of Veterinary Medicine, University of Wisconsin, Madison, WI, United States; Marsico Lung Institute, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Department of Pathology, National Institute of Infectious Diseases, Tokyo, Japan; Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, United States; Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, Japan
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Hou Y.J.,Chiba S.,Halfmann P.,et al. SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo[J],2020,370(6523).
APA Hou Y.J..,Chiba S..,Halfmann P..,Ehre C..,Kuroda M..,...&Baric R.S..(2020).SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo.Science,370(6523).
MLA Hou Y.J.,et al."SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo".Science 370.6523(2020).
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