SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo

被引：541

作者：

Hou, Yixuan J. ^{[1
]}

Chiba, Shiho ^{[2
]}

Halfmann, Peter ^{[2
]}

Ehre, Camille ^{[3
]}

Kuroda, Makoto ^{[2
]}

Dinnon, Kenneth H. ^{[4
]}

Leist, Sarah R. ^{[1
]}

Schafer, Alexandra ^{[1
]}

Nakajima, Noriko ^{[5
]}

Takahashi, Kenta ^{[5
]}

Lee, Rhianna E. ^{[3
]}

Mascenik, Teresa M. ^{[3
]}

Graham, Rachel ^{[1
]}

Edwards, Caitlin E. ^{[1
]}

Tse, Longping, V ^{[1
]}

Okuda, Kenichi ^{[3
]}

Markmann, Alena J. ^{[6
]}

Bartelt, Luther ^{[6
]}

de Silva, Aravinda ^{[4
]}

Margolis, David M. ^{[1
,4
,6
]}

Boucher, Richard C. ^{[3
]}

Randell, Scott H. ^{[3
]}

Suzuki, Tadaki ^{[5
]}

Gralinski, Lisa E. ^{[1
]}

Kawaoka, Yoshihiro ^{[2
,7
]}

Baric, Ralph S. ^{[1
,4
]}

机构：

[1] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27515 USA

[2] Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Influenza Res Inst, Madison, WI 53706 USA

[3] Univ N Carolina, Marsico Lung Inst, Chapel Hill, NC 27515 USA

[4] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27515 USA

[5] Natl Inst Infect Dis, Dept Pathol, Tokyo, Japan

[6] Univ N Carolina, Dept Med, Chapel Hill, NC 27515 USA

[7] Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Div Virol, Tokyo, Japan

来源：

SCIENCE | 2020年 / 370卷 / 6523期

基金：

美国国家卫生研究院;

关键词：

SARS CORONAVIRUS; EVOLUTION; ADAPTATION; FIDELITY; VIRUS; SPIKE; MODEL; MERS;

D O I：

10.1126/science.abe8499

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

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.

引用

页码：1464 / 1468

页数：5

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