Virological characteristics of the SARS-CoV-2 Omicron BA.2 subvariants, including BA.4 and BA.5

被引：160

作者：

Kimura, Izumi ^{[1
]}

Yamasoba, Daichi ^{[1
,2
]}

Tamura, Tomokazu ^{[3
]}

Nao, Naganori ^{[4
,5
]}

Suzuki, Tateki ^{[6
]}

Oda, Yoshitaka ^{[7
]}

Mitoma, Shuya ^{[8
]}

Ito, Jumpei ^{[1
]}

Nasser, Hesham ^{[9
,10
]}

Zahradnik, Jiri ^{[11
]}

Uriu, Keiya ^{[1
,12
]}

Fujita, Shigeru ^{[1
,12
]}

Kosugi, Yusuke ^{[1
,12
]}

Wang, Lei ^{[7
,13
]}

Tsuda, Masumi ^{[13
,17
]}

Kishimoto, Mai ^{[14
]}

Ito, Hayato ^{[3
]}

Suzuki, Rigel ^{[3
]}

Shimizu, Ryo ^{[9
]}

Begum, Mst Monira ^{[9
]}

Yoshimatsu, Kumiko ^{[15
]}

Kimura, Kanako Terakado ^{[6
]}

Sasaki, Jiei ^{[6
]}

Sasaki-Tabata, Kaori ^{[16
]}

Yamamoto, Yuki ^{[17
]}

Nagamoto, Tetsuharu ^{[17
]}

Kanamune, Jun ^{[17
]}

Kobiyama, Kouji ^{[18
,19
]}

Asakura, Hiroyuki ^{[20
]}

Nagashima, Mami ^{[20
]}

Sadamasu, Kenji ^{[20
]}

Yoshimura, Kazuhisa ^{[20
]}

Shirakawa, Kotaro ^{[21
]}

Takaori-Kondo, Akifumi ^{[21
]}

Kuramochi, Jin ^{[22
,23
]}

Schreiber, Gideon ^{[11
]}

Ishii, Ken J. ^{[18
,19
]}

Hashiguchi, Takao ^{[6
]}

Ikeda, Terumasa ^{[9
]}

Saito, Akatsuki ^{[8
,24
,25
]}

Fukuhara, Takasuke ^{[3
]}

Tanaka, Shinya ^{[7
,13
]}

Matsuno, Keita ^{[5
,26
,27
]}

Sato, Kei ^{[1
,12
,19
,28
,29
,30
,31
]}

机构：

[1] Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Div Syst Virol, Tokyo, Japan

[2] Kobe Univ, Fac Med, Kobe, Hyogo, Japan

[3] Hokkaido Univ, Grad Sch Med, Dept Microbiol & Immunol, Sapporo, Hokkaido, Japan

[4] Hokkaido Univ, Int Inst Zoonosis Control, Div Int Res Promot, Sapporo, Hokkaido, Japan

[5] Hokkaido Univ, One Hlth Res Ctr, Sapporo, Hokkaido, Japan

[6] Kyoto Univ, Inst Life & Med Sci, Lab Med Virol, Kyoto, Japan

[7] Hokkaido Univ, Fac Med, Dept Canc Pathol, Sapporo, Hokkaido, Japan

[8] Univ Miyazaki, Fac Agr, Dept Vet Sci, Miyazaki, Japan

[9] Kumamoto Univ, Joint Res Ctr Human Retrovirus Infect, Div Mol Virol & Genet, Kumamoto, Japan

[10] Suez Canal Univ, Fac Med, Dept Clin Pathol, Ismailia, Egypt

[11] Weizmann Inst Sci, Dept Biomol Sci, Rehovot, Israel

[12] Univ Tokyo, Grad Sch Med, Tokyo, Japan

[13] Hokkaido Univ, Inst Chem React Design & Discovery WPI ICReDD, Sapporo, Hokkaido, Japan

[14] Hokkaido Univ, Int Inst Zoonosis Control, Div Mol Pathobiol, Sapporo, Hokkaido, Japan

[15] Hokkaido Univ, Inst Genet Med, Sapporo, Hokkaido, Japan

[16] Kyushu Univ, Grad Sch Pharmaceut Sci, Dept Med Sci, Fukuoka, Japan

[17] HiLung Inc, Kyoto, Japan

[18] Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Div Vaccine Sci, Tokyo, Japan

[19] Univ Tokyo, Int Vaccine Design Ctr, Inst Med Sci, Tokyo, Japan

[20] Tokyo Metropolitan Inst Publ Hlth, Tokyo, Japan

[21] Kyoto Univ, Grad Sch Med, Dept Hematol & Oncol, Kyoto, Japan

[22] Interpk Kuramochi Clin, Utsunomiya, Tochigi, Japan

[23] Tokyo Med & Dent Univ, Dept Global Hlth Promot, Tokyo, Japan

[24] Univ Miyazaki, Ctr Anim Dis Control, Miyazaki, Japan

[25] Univ Miyazaki, Grad Sch Med & Vet Med, Miyazaki, Japan

[26] Hokkaido Univ, Int Inst Zoonosis Control, Int Collaborat Unit, Sapporo, Hokkaido, Japan

[27] Hokkaido Univ, Int Inst Zoonosis Control, Div Risk Anal & Management, Sapporo, Hokkaido, Japan

[28] Univ Tokyo, Int Res Ctr Infect Dis, Inst Med Sci, Tokyo, Japan

[29] Univ Tokyo, Grad Sch Frontier Sci, Kashiwa, Chiba, Japan

[30] Kumamoto Univ, Joint Res Ctr Human Retrovirus Infect, Collaborat Unit Infect, Kumamoto, Japan

[31] Japan Sci & Technol Agcy, CREST, Kawaguchi, Saitama, Japan

来源：

CELL | 2022年 / 185卷 / 21期

关键词：

EXPRESSION; ALIGNMENT; CELLS; L452R; TOOL;

D O I：

10.1016/j.cell.2022.09.018

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

After the global spread of the SARS-CoV-2 Omicron BA.2, some BA.2 subvariants, including BA.2.9.1, BA.2.11, BA.2.12.1, BA.4, and BA.5, emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these BA.2 subvariants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1/2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. We further provided the structure of the BA.4/5 spike receptor-binding domain that binds to human ACE2 and considered how the substitutions in the BA.4/5 spike play roles in ACE2 binding and immune evasion. Moreover, experiments using hamsters suggested that BA.4/5 is more pathogenic than BA.2. Our multiscale investigations suggest that the risk of BA.2 subvariants, particularly BA.4/5, to global health is greater than that of original BA.2.

引用

页码：3992 / +

页数：33

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