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Endogenous IFITMs boost SARS-coronavirus 1 and 2 replication whereas overexpression inhibits infection by relocalizing ACE2.
iScience. 2023 Apr 21; 26(4):106395.I

Abstract

Opposing effects of interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) on SARS-CoV-2 infection have been reported. The reasons for this are unclear and the role of IFITMs in infection of other human coronaviruses (hCoVs) remains poorly understood. Here, we demonstrate that endogenous expression of IFITM2 and/or IFITM3 is critical for efficient replication of SARS-CoV-1, SARS-CoV-2 and hCoV-OC43 but has little effect on MERS-, NL63-and 229E-hCoVs. In contrast, overexpression of IFITMs inhibits all these hCoVs, and the corresponding spike-containing pseudo-particles, except OC43, which is enhanced by IFITM3. We further demonstrate that overexpression of IFITMs impairs cell surface expression of ACE2 representing the entry receptor of SARS-CoVs and hCoV-NL63 but not hCoV-OC43. Our results explain the inhibitory effects of artificial IFITM overexpression on ACE2-tropic SARS-CoVs and show that three hCoVs, including major causative agents of severe respiratory disease, hijack IFITMs for efficient infection of human cells.

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Authors+Show Affiliations

Institute of Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany.

Institute of Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany.

Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.

Institute of Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany.

Institute of Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany.

Institute of Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany.

Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany.

Institute of Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany.

Institute of Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany.

Institute of Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany.

Institute of Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany.

Institute of Virology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, 10117 Berlin, Germany. German Centre for Infection Research (DZIF), Associated Partner Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.

Institute of Molecular Virology, Ulm University Medical Centre, 89081 Ulm, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

36968088

Citation

Xie, Qinya, et al. "Endogenous IFITMs Boost SARS-coronavirus 1 and 2 Replication Whereas Overexpression Inhibits Infection By Relocalizing ACE2." IScience, vol. 26, no. 4, 2023, p. 106395.

Xie Q, Bozzo CP, Eiben L, et al. Endogenous IFITMs boost SARS-coronavirus 1 and 2 replication whereas overexpression inhibits infection by relocalizing ACE2. iScience. 2023;26(4):106395.

Xie, Q., Bozzo, C. P., Eiben, L., Noettger, S., Kmiec, D., Nchioua, R., Niemeyer, D., Volcic, M., Lee, J. H., Zech, F., Sparrer, K. M. J., Drosten, C., & Kirchhoff, F. (2023). Endogenous IFITMs boost SARS-coronavirus 1 and 2 replication whereas overexpression inhibits infection by relocalizing ACE2. IScience, 26(4), 106395. https://doi.org/10.1016/j.isci.2023.106395

Xie Q, et al. Endogenous IFITMs Boost SARS-coronavirus 1 and 2 Replication Whereas Overexpression Inhibits Infection By Relocalizing ACE2. iScience. 2023 Apr 21;26(4):106395. PubMed PMID: 36968088.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Endogenous IFITMs boost SARS-coronavirus 1 and 2 replication whereas overexpression inhibits infection by relocalizing ACE2. AU - Xie,Qinya, AU - Bozzo,Caterina Prelli, AU - Eiben,Laura, AU - Noettger,Sabrina, AU - Kmiec,Dorota, AU - Nchioua,Rayhane, AU - Niemeyer,Daniela, AU - Volcic,Meta, AU - Lee,Jung-Hyun, AU - Zech,Fabian, AU - Sparrer,Konstantin M J, AU - Drosten,Christian, AU - Kirchhoff,Frank, Y1 - 2023/03/13/ PY - 2022/10/19/received PY - 2023/01/03/revised PY - 2023/03/08/accepted PY - 2023/3/27/entrez PY - 2023/3/28/pubmed PY - 2023/3/28/medline KW - Immunity KW - Protein KW - Virology SP - 106395 EP - 106395 JF - iScience JO - iScience VL - 26 IS - 4 N2 - Opposing effects of interferon-induced transmembrane proteins (IFITMs 1, 2 and 3) on SARS-CoV-2 infection have been reported. The reasons for this are unclear and the role of IFITMs in infection of other human coronaviruses (hCoVs) remains poorly understood. Here, we demonstrate that endogenous expression of IFITM2 and/or IFITM3 is critical for efficient replication of SARS-CoV-1, SARS-CoV-2 and hCoV-OC43 but has little effect on MERS-, NL63-and 229E-hCoVs. In contrast, overexpression of IFITMs inhibits all these hCoVs, and the corresponding spike-containing pseudo-particles, except OC43, which is enhanced by IFITM3. We further demonstrate that overexpression of IFITMs impairs cell surface expression of ACE2 representing the entry receptor of SARS-CoVs and hCoV-NL63 but not hCoV-OC43. Our results explain the inhibitory effects of artificial IFITM overexpression on ACE2-tropic SARS-CoVs and show that three hCoVs, including major causative agents of severe respiratory disease, hijack IFITMs for efficient infection of human cells. SN - 2589-0042 UR - https://www.unboundmedicine.com/medline/citation/36968088/Endogenous_IFITMs_boost_SARS_coronavirus_1_and_2_replication_whereas_overexpression_inhibits_infection_by_relocalizing_ACE2_ DB - PRIME DP - Unbound Medicine ER -