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加利福尼亚州一种携带L452R刺突蛋白突变的新型严重急性呼吸综合征冠状病毒2(SARS-CoV-2)变体的传播、传染性及抗体中和作用

Transmission, infectivity, and antibody neutralization of an emerging SARS-CoV-2 variant in California carrying a L452R spike protein mutation.

作者信息

Deng Xianding, Garcia-Knight Miguel A, Khalid Mir M, Servellita Venice, Wang Candace, Morris Mary Kate, Sotomayor-González Alicia, Glasner Dustin R, Reyes Kevin R, Gliwa Amelia S, Reddy Nikitha P, Martin Claudia Sanchez San, Federman Scot, Cheng Jing, Balcerek Joanna, Taylor Jordan, Streithorst Jessica A, Miller Steve, Kumar G Renuka, Sreekumar Bharath, Chen Pei-Yi, Schulze-Gahmen Ursula, Taha Taha Y, Hayashi Jennifer, Simoneau Camille R, McMahon Sarah, Lidsky Peter V, Xiao Yinghong, Hemarajata Peera, Green Nicole M, Espinosa Alex, Kath Chantha, Haw Monica, Bell John, Hacker Jill K, Hanson Carl, Wadford Debra A, Anaya Carlos, Ferguson Donna, Lareau Liana F, Frankino Phillip A, Shivram Haridha, Wyman Stacia K, Ott Melanie, Andino Raul, Chiu Charles Y

机构信息

Department of Laboratory Medicine, University of California San Francisco, California, USA.

UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, California, USA.

出版信息

medRxiv. 2021 Mar 9:2021.03.07.21252647. doi: 10.1101/2021.03.07.21252647.

Abstract

We identified a novel SARS-CoV-2 variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California. Named B.1.427/B.1.429 to denote its 2 lineages, the variant emerged around May 2020 and increased from 0% to >50% of sequenced cases from September 1, 2020 to January 29, 2021, exhibiting an 18.6-24% increase in transmissibility relative to wild-type circulating strains. The variant carries 3 mutations in the spike protein, including an L452R substitution. Our analyses revealed 2-fold increased B.1.427/B.1.429 viral shedding in vivo and increased L452R pseudovirus infection of cell cultures and lung organoids, albeit decreased relative to pseudoviruses carrying the N501Y mutation found in the B.1.1.7, B.1.351, and P.1 variants. Antibody neutralization assays showed 4.0 to 6.7-fold and 2.0-fold decreases in neutralizing titers from convalescent patients and vaccine recipients, respectively. The increased prevalence of a more transmissible variant in California associated with decreased antibody neutralization warrants further investigation.

摘要

我们通过对加利福尼亚州44个县的2172份鼻拭子/鼻咽拭子样本进行病毒全基因组测序,鉴定出一种新型严重急性呼吸综合征冠状病毒2(SARS-CoV-2)变体。该变体被命名为B.1.427/B.1.429以表示其两个谱系,于2020年5月左右出现,从2020年9月1日至2021年1月29日,在测序病例中的占比从0%增至超过50%,相对于野生型流行毒株,其传播性增加了18.6%-24%。该变体在刺突蛋白上携带3个突变,包括L452R替换。我们的分析显示,B.1.427/B.1.429在体内的病毒脱落增加了2倍,并且细胞培养物和肺类器官对携带L452R的假病毒感染增加,尽管相对于在B.1.1.7、B.1.351和P.1变体中发现的携带N501Y突变的假病毒有所减少。抗体中和试验表明,康复患者和疫苗接种者的中和滴度分别降低了4.0至6.7倍和2.0倍。在加利福尼亚州,一种传播性更强的变体的流行率增加且抗体中和作用降低,这值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b5ff/7987058/c9562a947da7/nihpp-2021.03.07.21252647-f0001.jpg

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