Whole-genome sequencing of SARS-CoV-2 Omicron variant strains isolated from pharyngeal swab samples in Shandong province
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摘要:
目的 对一起新型冠状病毒（SARS-CoV-2）奥密克戎（Omicron）变异株引起的疫情感染者咽拭子样本进行全基因组测序分析，为新冠病毒感染疫情防控提供参考依据。 方法 利用高通量测序技术对2022年4月山东省某县级市4例SARS-CoV-2感染者咽拭子样本进行全基因组测序，利用MEGA 7.0.14软件分析病毒同源性并构建进化树、分析变异位点等。 结果 4条SARS-CoV-2全基因组序列与参考株wuhan-hu-1相比同源性为99.76 %～99.77 %，在进化树上均位于奥密克戎BA.2进化分支；均发生多个基因位点变异和缺失，其中，A28271T变异致使N翻译起始区的 – 3位核苷酸由A变异为T；S蛋白LPP24-26缺失致使双色氨酸（WW）结构域的潜在结合基序PPAY25-28丢失。 结论 Omicron变异株出现大量变异位点，这些变异位点或与Omicron变异株传染性强、隐匿性高、引起临床严重程度低有一定关系。 Abstract:Objective To conduct whole genome sequencing of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) Omicron variant strains isolated from patients of a coronavirus disease 2019 (COVID-19) epidemic in Shandong province for effective control of COVID-19 epidemic. Methods High-throughput sequencing technology was used to sequence the whole genome of SARS-CoV-2 Omicron variant strains isolated from pharyngeal swab samples collected from four COVID-19 cases in a prefecture of Shandong province in April 2022. MEGA 7.0.14 software was adopted in homology and mutation analysis and evolutionary tree construction of the viral strains. Results The whole genome sequences of the four SARS-CoV-2 variants have 99.76% – 99.77% homology with the reference strain Wuhan-hu-1, and they are all located in the BA.2 clade of Omicron variant on the evolutionary tree. The 4 sequences all had multiple genetic loci variations and deletions; of which, A28271T mutation caused the -3 nucleotide of N gene translation initiation region changing from A to T and the deletion of amino acid from 24 to 26 of S protein resulted in the loss of the potential binding motif PPAY25-28 of the WW domain. Conclusion Several gene site mutants occurred in SARS-CoV-2 Omicron variants and the mutants may associate with highly infectious and camouflage of the variants and mild clinical symptoms of the viral infection. 1) （解翠华同为本文第一作者） -
表 1 新冠病毒基因变异分析
基因名称 蛋白名称 基因变异位点 蛋白变异位点 5'UTR C241T ORF1ab NSP1 T670G、C2790T、C3037T、G4184A C4321TC6578T■ S135R；M85缺失● PLpro A8658G●、T9200C●、C9344T、A9424G、C9534T、C9866T T24R、G489S、L1287F■ NSP4 C10029T、C10198T、G10447A、C10449A、C12781T▲■ K35R●、F216L●、L264F、T327R、L438F、T492I 3CLpro C12880T、C14408T、C14724T、C15714T、C17410T P132F NSP6 A18163G、G19900A、C19955T、A20055G；ATG 518-520缺失● SGF106-108缺失 RdRp 11288-11296缺失 P323L helicase R392C NSP14 I42V NSP15 A94T、T112I S S C21618T、G21987A、T22200G、G22578A、C22674T
T22679C、C22686T、A22688G、G22775A、A22786C
G22813T、T22882G、G22992A、C22995A、A23013C
A23040G、A23055G、A23063T、T23075C、A23403G
C23525T、T23599G、C23604A、C23673T▲■、C23854A
G23948T、A24424T、T24469A、C25000T、21633-21641缺失T19I、A27S、G142D、V213G、G339D、S371F、S373P、S375F
T376A、D405N、R408S、K417N、N440K、S477N、T478K
E484A、Q493R、Q498R、N501Y、Y505H、D614G、H655Y
N679K、P681H、S704L▲■、N764K、D796Y、Q954H、N969K
LPP24-26缺失ORF3a ORF3a C25584T、C26060T T223I E E C26270T T9I M M C26577G、G26709A、C26858T Q19E、A63T ORF6 ORF6 A27259C、G27382C、A27383T、T27384C D61L ORF7b ORF7b C27807T ORF8 ORF8 A27898T K2I N翻译起始区 A28271T N N C28311T、C28606T、G28881A、G28882A、G28883C
A29510C、28362-28370缺失P13L、R203K、G204R、S413R、ERS31-33缺失 注：未标注代表4条序列共有变异；●代表感染者2序列变异；▲代表感染者3序列变异；■代表感染者4序列变异。 
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