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, Sanchez San Martin Claudia, Federman Scot, Cheng Jing, Balcerek Joanna, Taylor Jordan, Streithorst Jessica A, Miller Steve, Sreekumar Bharath, Chen Pei-Yi, Schulze-Gahmen Ursula, Taha Taha Y, Hayashi Jennifer M, Simoneau Camille R, Kumar G Renuka, 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, Frankino Phillip A, Shivram Haridha, Lareau Liana F, Wyman Stacia K, Ott Melanie, Andino Raul, Chiu Charles Y
Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94158, USA; UCSF-Abbott Viral Diagnostics and Discovery Center, San Francisco, CA 94158, USA.
Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94143, USA.
Cell. 2021 Jun 24;184(13):3426-3437.e8. doi: 10.1016/j.cell.2021.04.025. Epub 2021 Apr 20.
We identified an emerging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant by viral whole-genome sequencing of 2,172 nasal/nasopharyngeal swab samples from 44 counties in California, a state in the western United States. Named B.1.427/B.1.429 to denote its two lineages, the variant emerged in May 2020 and increased from 0% to >50% of sequenced cases from September 2020 to January 2021, showing 18.6%-24% increased transmissibility relative to wild-type circulating strains. The variant carries three mutations in the spike protein, including an L452R substitution. We found 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 common to variants B.1.1.7, B.1.351, and P.1. Antibody neutralization assays revealed 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 exhibiting decreased antibody neutralization warrants further investigation.
我们通过对来自美国西部加利福尼亚州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，鉴定出一种新出现的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月出现，从2020年9月到2021年1月，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三个突变，包括L452R替代。我们发现，B.1.427/B.1.429在体内的病毒载量增加了2倍，在细胞培养物和肺类器官中L452R假病毒感染增加，尽管相对于携带B.1.1.7、B.1.351和P.1变体共有的N501Y突变的假病毒有所降低。抗体中和试验显示，康复患者和疫苗接种者的中和效价分别降低了4.0至6.7倍和2.0倍。在加利福尼亚州，一种传播性更强但抗体中和作用降低的变体的流行率增加，这值得进一步研究。
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