周莎,陈龙,屈雅丽,吕秋莹,张仁利,姚相杰,孟君,张晓敏,吴春利,孙颖,刘慧,魏欣仪,陈建成,李诗敏,朱灿,卢清菊,钟庭珊,陈慧,胡雪婷,陈妙媚,黄小丽,何雅青

• 1:南华大学公共卫生学院
• 2:深圳市疾病预防控制中心病原微生物检测所
• 3:南方医科大学公共卫生学院流行病学系
• 4:深圳市疾病预防控制中心传染病预防控制所

摘要(Abstract)：

新型冠状病毒（SARS-CoV-2）BA.2亚谱系BA.2.12.1表现出令人担忧的传播能力。为了了解深圳本地与输入的BA.2亚谱系分布与遗传特征，本研究对2022年1-6月深圳市BA.2亚系变异株进行了全基因组序列分析。通过高通量测序，本研究获得了155例本土、30例输入共185株覆盖度98%以上的BA.2亚型毒株的基因组序列。185株BA.2亚型毒株可分为BA.2.2、BA.2.3、BA.2.9、BA.2.10、BA.2.10.1、BA.2.12.1和BA.2.29七种亚型，其中BA.2.2占比最高（92.97%, 172/185），其他亚型占比从高到低依次为BA.2.10.1 (2.70%, 5/185)、BA.2.10 (1.62%, 3/185)、BA.2.9 (1.08%, 2/185)、BA.2.3 (0.54%, 1/185)、BA.2.12.1(0.54%, 1/185)及BA.2.29(0.54%, 1/185)。172株BA.2.2亚型变异株中，本土及中国香港输入各153株（88.95%）和19株（11.05%）。序列比较分析发现，153株深圳本土BA.2.2毒株与19株中国香港输入BA.2.2毒株共享69个核苷酸变异位点和52个氨基酸变异位点（不包括缺失突变）。根据单核苷酸变异位点特征，153株深圳本土BA.2.2毒株至少可以分为6条传播链。与特征性突变相比，1株美国输入的受关注BA.2.12.1变异株在N区多了一个P383L氨基酸变异位点。深圳本地与输入的BA.2亚系变异株呈现出了高基因组多样性特征，开展SARS-CoV-2关切变异株与亚谱系毒株的分子监测，对新型冠状病毒感染（COVID-19）疫情的溯源与防控具有重要意义。

关键词(KeyWords)： 新型冠状病毒;BA.2亚系;深圳;基因组序列;溯源

Abstract:

Keywords:

基金项目(Foundation): 深圳市科技创新委员会技术攻关重点项目（项目号：JSGG20200225152648408）,题目：基于SARS-CoV-2冠状病毒表面Spike蛋白的早期快检技术研发;深圳市科技创新委员会技术攻关重点项目（项目号：JSGG20210901145004012）,题目：新冠病毒变异株快速检测试剂盒关键技术研发;深圳市科技创新委员会技术攻关重点项目（项目号：JSGG20220606141401003）,题目：抗疫专2022055新冠病毒S蛋白抗原自测试纸条及材料关键技术研发~~

作者(Author): 周莎,陈龙,屈雅丽,吕秋莹,张仁利,姚相杰,孟君,张晓敏,吴春利,孙颖,刘慧,魏欣仪,陈建成,李诗敏,朱灿,卢清菊,钟庭珊,陈慧,胡雪婷,陈妙媚,黄小丽,何雅青

DOI: 10.13242/j.cnki.bingduxuebao.004328

参考文献(References)：

• [1] Lu R, Zhao X, Li J, Niu P, Yang B, Wu H, Wang W, Song H, Huang B, Zhu N, Bi Y, Ma X, Zhan F,Wang L, Hu T, Zhou H, Hu Z, Zhou W, Zhao L,Chen J, Meng Y, Wang J, Lin Y, Yuan J, Xie Z, Ma J, Liu W J, Wang D, Xu W, Holmes E C, Gao G F,Wu G, Chen W, Shi W, Tan W. Genomic characterisation and epidemiology of 2019 novel coronavirus:implications for virus origins and receptor binding[J]. Lancet, 2020, 395(10224):565-574.
• [2] Chen L, Liu W, Zhang Q, Xu K, Ye G, Wu W, Sun Z, Liu F, Wu K, Zhong B, Mei Y, Zhang W, Chen Y, Li Y, Shi M, Lan K, Liu Y. RNA based mNGS approach identifies a novel human coronavirus from two individual pneumonia cases in 2019 Wuhan outbreak[J].Emerg Microbes Infect, 2020, 9(1):313-319.
• [3] Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, Schiergens T S, Herrler G,Wu N H, Nitsche A, Müller M A, Drosten C,P?hlmann S. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor[J]. Cell, 2020, 181(2):271-280.e278.
• [4] Ramesh S, Govindarajulu M, Parise R S, Neel L,Shankar T, Patel S, Lowery P, Smith F,Dhanasekaran M, Moore T. Emerging SARS-CoV-2variants:a review of its mutations, its implications and vaccine efficacy[J]. Vaccines(Basel), 2021, 9(10).
• [5] Walls A C, Park Y J, Tortorici M A, Wall A,McGuire A T, Veesler D. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein[J]. Cell, 2020, 181(2):281-292.e286.
• [6] Tracking SARS-CoV-2 variants.[EB/OL]. https：//www.who.int/activities/tracking-SARS-CoV-2-variants.
• [7] Callaway E. Why does the Omicron sub-variant spread faster than the original?[J]. Nature, 2022, 602(7898):556-557.
• [8] Chen J, Wei G W. Omicron BA.2(B.1.1.529.2):High Potential for Becoming the Next Dominant Variant[J]. J Phys Chem Lett, 2022, 13(17):3840-3849.
• [9] Cao Y, Yisimayi A, Jian F, Song W, Xiao T, Wang L, Du S, Wang J, Li Q, Chen X, Yu Y, Wang P,Zhang Z, Liu P, An R, Hao X, Wang Y, Wang J,Feng R, Sun H, Zhao L, Zhang W, Zhao D, Zheng J,Yu L, Li C, Zhang N, Wang R, Niu X, Yang S, Song X, Chai Y, Hu Y, Shi Y, Zheng L, Li Z, Gu Q, Shao F, Huang W, Jin R, Shen Z, Wang Y, Wang X, Xiao J, Xie X S. BA. 2.12.1, BA. 4 and BA. 5 escape antibodies elicited by Omicron infection[J]. Nature,2022.
• [10]Link-Gelles R, Levy M E, Gaglani M, Irving S A,Stockwell M, Dascomb K, DeSilva M B, Reese S E,Liao I C, Ong T C, Grannis S J, McEvoy C, Patel P,Klein N P, Hartmann E, Stenehjem E, Natarajan K,Naleway A L, Murthy K, Rao S, Dixon B E,Kharbanda A B, Akinseye A, Dickerson M, Lewis N,Grisel N, Han J, Barron M A, Fadel W F, Dunne M M, Goddard K, Arndorfer J, Konatham D, Valvi N R,Currey J C, Fireman B, Raiyani C, Zerbo O, SloanAagard C, Ball S W, Thompson M G, Tenforde M W.Effectiveness of 2, 3, and 4 COVID-19 mRNA Vaccine Doses Among Immunocompetent Adults During Periods when SARS-CoV-2 Omicron BA. 1 and BA. 2/BA. 2.12.1 Sublineages Predominated-VISION Network, 10 States, December 2021-June 2022[J].MMWR Morb Mortal Wkly Rep, 2022, 71(29):931-939.
• [11]新型冠状病毒肺炎诊疗方案（试行第九版）[EB/OL].http：//www. nhc. gov. cn/yzygj/s7653p/202203/b74ade1ba4494583805a3d2e40093d88.shtml.
• [12]McCallum M, De Marco A, Lempp F A, Tortorici M A, Pinto D, Walls A C, Beltramello M, Chen A, Liu Z, Zatta F, Zepeda S, di Iulio J, Bowen J E, MontielRuiz M, Zhou J, Rosen L E, Bianchi S, Guarino B,Fregni C S, Abdelnabi R, Foo S C, Rothlauf P W,Bloyet L M, Benigni F, Cameroni E, Neyts J, Riva A,Snell G, Telenti A, Whelan S P J, Virgin H W, Corti D, Pizzuto M S, Veesler D. N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2[J]. Cell, 2021, 184(9):2332-2347.e2316.
• [13]McCallum M, Czudnochowski N, Rosen L E, Zepeda S K, Bowen J E, Walls A C, Hauser K, Joshi A,Stewart C, Dillen J R, Powell A E, Croll T I, Nix J,Virgin H W, Corti D, Snell G, Veesler D. Structural basis of SARS-CoV-2 Omicron immune evasion and receptor engagement[J]. Science, 2022, 375(6583):864-868.
• [14]Mannar D, Saville J W, Zhu X, Srivastava S S,Berezuk A M, Tuttle K S, Marquez A C, Sekirov I,Subramaniam S. SARS-CoV-2 Omicron variant:Antibody evasion and cryo-EM structure of spike proteinACE2 complex[J]. Science, 2022, 375(6582):760-764.
• [15]Verma J, Subbarao N. Insilico study on the effect of SARS-CoV-2 RBD hotspot mutants′interaction with ACE2 to understand the binding affinity and stability[J].Virology, 2021, 561:107-116.
• [16]Han P, Li L, Liu S, Wang Q, Zhang D, Xu Z, Han P, Li X, Peng Q, Su C, Huang B, Li D, Zhang R,Tian M, Fu L, Gao Y, Zhao X, Liu K, Qi J, Gao G F, Wang P. Receptor binding and complex structures of human ACE2 to spike RBD from omicron and delta SARS-CoV-2[J]. Cell, 2022, 185(4):630-640.e610.
• [17]Wrobel A G, Benton D J, Roustan C, Borg A, Hussain S, Martin S R, Rosenthal P B, Skehel J J, Gamblin S J. Evolution of the SARS-CoV-2 spike protein in the human host[J]. Nat Commun, 2022, 13(1):1178.
• [18]Motozono C, Toyoda M, Zahradnik J, Saito A, Nasser H, Tan T S, Ngare I, Kimura I, Uriu K, Kosugi Y,Yue Y, Shimizu R, Ito J, Torii S, Yonekawa A,Shimono N, Nagasaki Y, Minami R, Toya T, Sekiya N, Fukuhara T, Matsuura Y, Schreiber G, Ikeda T,Nakagawa S, Ueno T, Sato K. SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity[J]. Cell Host Microbe, 2021, 29(7):1124-1136.e1111.
• [19]Kimura I, Kosugi Y, Wu J, Zahradnik J, Yamasoba D,Butlertanaka E P, Tanaka Y L, Uriu K, Liu Y,Morizako N, Shirakawa K, Kazuma Y, Nomura R,Horisawa Y, Tokunaga K, Ueno T, Takaori-Kondo A, Schreiber G, Arase H, Motozono C, Saito A,Nakagawa S, Sato K. The SARS-CoV-2 Lambda variant exhibits enhanced infectivity and immune resistance[J]. Cell Rep, 2022, 38(2):110218.
• [20]Chang C K, Sue S C, Yu T H, Hsieh C M, Tsai C K,Chiang Y C, Lee S J, Hsiao H H, Wu W J, Chang W L, Lin C H, Huang T H. Modular organization of SARS coronavirus nucleocapsid protein[J]. J Biomed Sci, 2006, 13(1):59-72.
• [21]Peng T Y, Lee K R, Tarn W Y. Phosphorylation of the arginine/serine dipeptide-rich motif of the severe acute respiratory syndrome coronavirus nucleocapsid protein modulates its multimerization, translation inhibitory activity and cellular localization[J]. Febs J, 2008, 275(16):4152-4163.
• [22]Mefsin Y M, Chen D, Bond H S, Lin Y, Cheung J K,Wong J Y, Ali S T, Lau E H Y, Wu P, Leung G M,Cowling B J. Epidemiology of infections with SARSCoV-2 Omicron BA. 2 Variant, Hong Kong, JanuaryMarch 2022[J]. Emerg Infect Dis, 2022, 28(9):1856-1858.
• [23]Hossain A, Akter S, Rashid A A, Khair S, Alam A.Unique mutations in SARS-CoV-2 Omicron subvariants′non-spike proteins:Potential impacts on viral pathogenesis and host immune evasion[J]. Microb Pathog, 2022, 170:105699.