Determination of the factors responsible for the tropism of SARS-CoV-2-related bat coronaviruses to
Rhinolophus
bat ACE2
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Published:2023-10-31
Issue:10
Volume:97
Page:
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ISSN:0022-538X
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Container-title:Journal of Virology
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language:en
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Short-container-title:J Virol
Author:
Fujita Shigeru12, Kosugi Yusuke12, Kimura Izumi1, Tokunaga Kenzo3, Ito Jumpei14, Sato Kei12456ORCID, Matsuno Keita7, Nao Naganori7, Sawa Hirofumi7, Tanaka Shinya7, Tsuda Masumi7, Wang Lei7, Oda Yoshikata7, Ferdous Zannatul7, Shishido Kenji7, Fukuhara Takasuke7, Tamura Tomokazu7, Suzuki Rigel7, Suzuki Saori7, Ito Hayato7, Kaku Yu, Misawa Naoko, Plianchaisuk Arnon, Guo Ziyi, Hinay Alfredo A., Uriu Keiya, Tolentino Jarel Elgin M., Chen Luo, Pan Lin, Suganami Mai, Chiba Mika, Yoshimura Ryo, Yasuda Kyoko, Iida Keiko, Ohsumi Naomi, Strange Adam P., Tanaka Shiho, Yoshimura Kazuhisa8, Sadamasu Kenji8, Nagashima Mami8, Asakura Hiroyuki8, Yoshida Isao8, Nakagawa So9, Takaori-Kondo Akifumi10, Nagata Kayoko10, Nomura Ryosuke10, Horisawa Yoshihito10, Tashiro Yusuke10, Kawai Yugo10, Takayama Kazuo10, Hashimoto Rina10, Deguchi Sayaka10, Watanabe Yukio10, Sakamoto Ayaka10, Yasuhara Naoko, Hashiguchi Takao10, Suzuki Tateki10, Kimura Kanako10, Sasaki Jiei10, Nakajima Yukari10, Yajima Hisano10, Irie Takashi11, Kawabata Ryoko11, Tabata Kaori12, Ikeda Terumasa13, Nasser Hesham13, Shimizu Ryo13, Monira Begum M. S. T.13, Jonathan Michael13, Mugita Yuka13, Takahashi Otowa13, Ichihara Kimiko13, Motozono Chihiro13, Ueno Takamasa13, Toyoda Mako13, Saito Akatsuki14, Shofa Maya14, Shibatani Yuki14, Nishiuchi Tomoko14, Shirakawa Kotaro10,
Affiliation:
1. Division of Systems Virology, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo , Tokyo, Japan 2. Graduate School of Medicine, The University of Tokyo , Tokyo, Japan 3. Department of Pathology, National Institute of Infectious Diseases , Tokyo, Japan 4. International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo , Tokyo, Japan 5. International Vaccine Design Center, The Institute of Medical Science, The University of Tokyo , Tokyo, Japan 6. Graduate School of Frontier Sciences, The University of Tokyo , Kashiwa, Japan 7. Hokkaido University , Sapporo, Japan 8. Tokyo Metropolitan Institute of Public Health , Shinjuku City, Japan 9. Tokai University , Shibuya City, Japan 10. Kyoto University , Kyoto, Japan 11. Hiroshima University , Hiroshima, Japan 12. Kyushu University , Fukuoka, Japan 13. Kumamoto University , Kumamoto, Japan 14. University of Miyazaki , Miyazaki, Japan
Abstract
ABSTRACT
Differences in host angiotensin converting enzyme 2 (ACE2) genes may affect the host range of SARS-CoV-2-related coronaviruses (SC2r-CoVs) and further determine the tropism of host ACE2 for the infection receptor. However, the factor(s) responsible for determining the host tropism of SC2r-CoVs, which may in part be determined by the tropism of host ACE2 usage, remains unclear. Here, we use the pseudoviruses with the spike proteins of two Laotian SC2r-CoVs, BANAL-20-236 and BANAL-20-52, and the cells expressing ACE2 proteins of eight different
Rhinolophus
bat species to show that these two spikes have different tropisms for
Rhinolophus
bat ACE2. Through structural analysis and cell culture experiments, we demonstrate that this tropism is determined by residue 493 of the spike and residues 31 and 35 of ACE2. Our results suggest that SC2r-CoVs exhibit differential ACE2 tropism, which may be driven by adaptation to different
Rhinolophus
bat ACE2 proteins.
IMPORTANCE
The efficiency of infection receptor use is the first step in determining the species tropism of viruses. After the coronavirus disease 2019 pandemic, a number of SARS-CoV-2-related coronaviruses (SC2r-CoVs) were identified in
Rhinolophus
bats, and some of them can use human angiotensin converting enzyme 2 (ACE2) for the infection receptor without acquiring additional mutations. This means that the potential of certain SC2r-CoVs to cause spillover from bats to humans is "off-the-shelf." However, both SC2r-CoVs and
Rhinolophus
bat species are highly diversified, and the host tropism of SC2r-CoVs remains unclear. Here, we focus on two Laotian SC2r-CoVs, BANAL-20-236 and BANAL-20-52, and determine how the tropism of SC2r-CoVs to
Rhinolophus
bat ACE2 is determined at the amino acid resolution level.
Funder
Japan Agency for Medical Research and Development Japan Science an Technology Agency Japan Society for the Promotion of Science
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
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