Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5
Author:
Kimura Izumi, Yamasoba Daichi, Tamura Tomokazu, Nao Naganori, Oda Yoshitaka, Mitoma Shuya, Ito Jumpei, Nasser Hesham, Zahradnik Jiri, Uriu Keiya, Fujita Shigeru, Kosugi Yusuke, Wang Lei, Tsuda Masumi, Kishimoto Mai, Ito Hayato, Suzuki Rigel, Shimizu Ryo, Begum MST Monira, Yoshimatsu Kumiko, Sasaki Jiei, Sasaki-Tabata Kaori, Yamamoto Yuki, Nagamoto Tetsuharu, Kanamune Jun, Kobiyama Kouji, Asakura Hiroyuki, Nagashima Mami, Sadamasu Kenji, Yoshimura Kazuhisa, Kuramochi Jin, Schreiber Gideon, Ishii Ken JORCID, Hashiguchi Takao, Ikeda Terumasa, Saito AkatsukiORCID, Fukuhara Takasuke, Tanaka ShinyaORCID, Matsuno Keita, Sato Kei,
Abstract
AbstractAfter the global spread of SARS-CoV-2 Omicron BA.2 lineage, some BA.2-related variants that acquire mutations in the L452 residue of spike protein, such as BA.2.9.1 and BA.2.13 (L452M), BA.2.12.1 (L452Q), and BA.2.11, BA.4 and BA.5 (L452R), emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these L452R/M/Q-bearing BA.2-related Omicron variants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1 and BA.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. Furthermore, infection experiments using hamsters indicated that BA.4/5 is more pathogenic than BA.2. Altogether, our multiscale investigations suggest that the risk of L452R/M/Q-bearing BA.2-related Omicron variants, particularly BA.4 and BA.5, to global health is potentially greater than that of original BA.2.HighlightsSpike L452R/Q/M mutations increase the effective reproduction number of BA.2BA.4/5 is resistant to the immunity induced by BA.1 and BA.2 infectionsBA.2.12.1 and BA.4/5 more efficiently spread in human lung cells than BA.2BA.4/5 is more pathogenic than BA.2 in hamsters
Publisher
Cold Spring Harbor Laboratory
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