The mutational dynamics of the SARS-CoV-2 virus in serial passages in vitro

作     者：Sissy Therese Sonnleitner Stefanie Sonnleitner Eva Hinterbichler Hannah Halbfurter Dominik BCKopecky Stephan Koblmüller Christian Sturmbauer Wilfried Posch Gernot Walder Sissy Therese Sonnleitner;Stefanie Sonnleitner;Eva Hinterbichler;Hannah Halbfurter;Dominik B.C.Kopecky;Stephan Koblmüller;Christian Sturmbauer;Wilfried Posch;Gernot Walder

作者机构：Dr.Gernot Walder GmbHMedical LaboratoryDepartment of VirologyAusservillgraten9931Austria Division of Hygiene and Medical MicrobiologyMedical University of InnsbruckInnsbruck6020Austria Institute of BiologyUniversity of GrazGraz8010Austria 

出 版 物：《Virologica Sinica》 (中国病毒学（英文版）)

年 卷 期：2022年第37卷第2期

页      面：198-207页

核心收录：

学科分类：0710[理学-生物学] 1007[医学-药学(可授医学、理学学位)] 100705[医学-微生物与生化药学] 1001[医学-基础医学(可授医学、理学学位)] 100103[医学-病原生物学] 10[医学] 

基　　金：the financial support of the Austrian Research Promotion Agency(FFG) Grant No.35863961 

主　　题：SARS-CoV-2 Whole genome sequencing(WGS) Mutational dynamics Adaptation Serial passage in vitro 

摘      要：Since its outbreak in 2019,Severe Acute Respiratory Syndrome Coronavirus 2(SARS-Co V-2)keeps surprising the medical community by evolving diverse immune escape mutations in a rapid and effective *** gain deeper insight into mutation frequency and dynamics,we isolated ten ancestral strains of SARS-Co V-2 and performed consecutive serial incubation in ten replications in a suitable and common cell line and subsequently analysed them using RT-q PCR and whole genome *** those lines we hoped to gain fundamental insights into the evolutionary capacity of SARS-Co V-2 in *** results identified a series of adaptive genetic changes,ranging from unique convergent substitutional mutations and hitherto undescribed *** region coding for spike proved to be a mutational hotspot,evolving a number of mutational changes including the already known substitutions at positions S:484 and S:*** discussed the evolution of all specific adaptations as well as possible reasons for the seemingly inhomogeneous potential of SARS-Co V-2 in the adaptation to cell *** combination of serial passage in vitro with whole genome sequencing uncovers the immense mutational potential of some SARS-Co V-2 *** observed genetic changes of SARS-Co V-2 in vitro could not be explained solely by selectively neutral mutations but possibly resulted from the action of directional selection accumulating favourable genetic changes in the evolving variants,along the path of increasing potency of the *** among a high number of quasi-species in the SARS-Co V-2 in vitro population gene pool may reinforce directional selection and boost the speed of evolutionary change.