Genomic monitoring of SARS-CoV-2 uncovers an Nsp1 deletion variant that modulates type I interferon response

Jing-wen Lin, Chao Tang, Han-cheng Wei, Baowen Du, Chuan Chen, Minjin Wang, Yongzhao Zhou, Ming-xia Yu, Lu Cheng, Suvi Kuivanen, Natacha S. Ogando, Lev Levanov, Yuancun Zhao, Chang-ling Li, Ran Zhou, Zhidan Li, Yiming Zhang, Ke Sun, Chengdi Wang, Li ChenXia Xiao, Xiuran Zheng, Sha-sha Chen, Ruirui Yang, Dan Zhang, Mengying Xu, Junwei Song, Danrui Wang, Yupeng Li, ShiKun Lei, Wanqin Zeng, Qingxin Yang, Ping He, Yaoyao Zhang, Lifang Zhou, Ling Cao, Feng Luo, Huayi Liu, Liping Wang, Fei Ye, Ming Zhang, Mengjiao Li, Xinqiong Li, Kaiju Li, Bowen Ke, Jiannan Xu, Huiping Yang, Shusen He, Ming Pan, Yichen Yan, Yi Zha, Lingyu Jiang, Changxiu Yu, Yingfen Liu, Zhiyong Xu, Qingfeng Li, Yongmei Jiang, Jiufeng Sun, Wei Hong, Hongping Wei, Guangwen Lu, Olli Vapalahti, Yunzi Luo, Yuquan Wei, Thomas Connor, Wenjie Tan, Eric J. Snijder, Teemu Smura, Weimin Li, Jia Geng, Binwu Ying, Lu Chen

Tutkimustuotos: LehtiartikkeliArticleScientificvertaisarvioitu

Abstrakti

The SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here, we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical phenotyping, and experimental validation to locate mutations of clinical importance. We identified 35 recurrent variants, some of which are associated with clinical phenotypes related to severity. One variant, containing a deletion in the Nsp1-coding region (Δ500-532), was found in more than 20% of our sequenced samples and associates with higher RT-PCR cycle thresholds and lower serum IFN-β levels of infected patients. Deletion variants in this locus were found in 37 countries worldwide, and viruses isolated from clinical samples or engineered by reverse genetics with related deletions in Nsp1 also induce lower IFN-β responses in infected Calu-3 cells. Taken together, our virologic surveillance characterizes recurrent genetic diversity and identified mutations in Nsp1 of biological and clinical importance, which collectively may aid molecular diagnostics and drug design.

AlkuperäiskieliEnglanti
Sivut489-502.e8
Sivumäärä22
JulkaisuCELL HOST AND MICROBE
Vuosikerta29
Numero3
Varhainen verkossa julkaisun päivämäärä29 tammikuuta 2021
DOI - pysyväislinkit
TilaJulkaistu - 10 maaliskuuta 2021
OKM-julkaisutyyppiA1 Julkaistu artikkeli, soviteltu

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