• Allen, E., Randolph, A., Bhangale, T., Dogra, P., Ohlson, M., Oshansky, C., Zamora, A., Shannon, J., Finkelstein, D., Dressen, A., Devincenzo, J., Caniza, M., Youngblood, B., Rosenberger, C., Thomas, P., 2017. SNP-mediated disruption of CTCF binding at the IFITM3 promoter is associated with risk of severe influenza in humans. Nat. Med. 23, 975-983.

  • Amini-Bavil-Olyaee, S., Choi, Y., Lee, J., Shi, M., Huang, I., Farzan, M., Jung, J., 2013. The antiviral effector IFITM3 disrupts intracellular cholesterol homeostasis to block viral entry. Cell Host Microbe 13, 452-464.

  • Bailey, C., Kondur, H., Huang, I., Farzan, M., 2013. Interferon-induced transmembrane protein 3 is a type II transmembrane protein. J. Biol. Chem. 288, 32184-32193.

  • Bailey, C.C., Huang, I.C., Kam, C., Farzan, M., 2012. Ifitm3 limits the severity of acute influenza in mice. PLoS Pathog. 8, e1002909.

  • Boonstra, S., Blijleven, J., Roos, W., Onck, P., Van Der Giessen, E., Van Oijen, A., 2018.Hemagglutinin-mediated membrane fusion:a biophysical perspective. Annu. Rev.Biophys. 47, 153-173.

  • Brass, A.L., Huang, I.C., Benita, Y., John, S.P., Krishnan, M.N., Feeley, E.M., Ryan, B.J., Weyer, J.L., Van Der Weyden, L., Fikrig, E., Adams, D.J., Xavier, R.J., Farzan, M., Elledge, S.J., 2009. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell 139, 1243-1254.

  • Buchrieser, J., Dufloo, J., Hubert, M., Monel, B., Planas, D., Rajah, M.M., Planchais, C., Porrot, F., Guivel-Benhassine, F., Van Der Werf, S., Casartelli, N., Mouquet, H., Bruel, T., Schwartz, O., 2021. Syncytia formation by SARS-CoV-2-infected cells.EMBO J. 40, e107405.

  • Cao, T.T., Du, S.W., Xu, W., Xing, B., Zhao, F., Wang, M.P., Zhu, Y.L., Bai, J.Y., Tian, Y.F., Liu, L.M., Zhao, C.Q., Zhou, Y.F., Li, C., Jin, N.Y., 2017. Establishment and functional analysis of MDCK cell line induced IFITM3 expression based on tet-on 3G system.Chem. J. Chin. Univ. 38, 770-777.

  • Chang, D., Cheng, S., Kantchev, E., Lin, C., Liu, Y., 2008. Membrane interaction and structure of the transmembrane domain of influenza hemagglutinin and its fusion peptide complex. BMC Biol. 6, 2.

  • Chemudupati, M., Kenney, A.D., Bonifati, S., Zani, A., Mcmichael, T.M., Wu, L., Yount, J.S., 2019. From APOBEC to ZAP:diverse mechanisms used by cellular restriction factors to inhibit virus infections. Biochimica et biophysica acta. Mol. Cell Res. 1866, 382-394.

  • Chesarino, N.M., Compton, A.A., Mcmichael, T.M., Kenney, A.D., Zhang, L., Soewarna, V., Davis, M., Schwartz, O., Yount, J.S., 2017. IFITM3 requires an amphipathic helix for antiviral activity. EMBO Rep. 18, 1740-1751.

  • Chesarino, N.M., Mcmichael, T.M., Hach, J.C., Yount, J.S., 2014. Phosphorylation of the antiviral protein interferon-inducible transmembrane protein 3 (IFITM3) dually regulates its endocytosis and ubiquitination. J. Biol. Chem. 289, 11986-11992.

  • Compton, A.A., Bruel, T., Porrot, F., Mallet, A., Sachse, M., Euvrard, M., Liang, C., Casartelli, N., Schwartz, O., 2014. IFITM proteins incorporated into HIV-1 virions impair viral fusion and spread. Cell Host Microbe 16, 736-747.

  • Coomer, C., Rahman, K., Compton, A., 2021. CD225 proteins:a family portrait of fusion regulators. Trends Genet. 37, 406-410.

  • Desai, T.M., Marin, M., Chin, C.R., Savidis, G., Brass, A.L., Melikyan, G.B., 2014. IFITM3 restricts influenza A virus entry by blocking the formation of fusion pores following virus-endosome hemifusion. PLoS Pathog. 10, e1004048.

  • Drouin, A., Migraine, J., Durand, M., Moreau, A., Burlaud-Gaillard, J., Beretta, M., Roingeard, P., Bouvin-Pley, M., Braibant, M., 2020. Escape of HIV-1 envelope glycoprotein from the restriction of infection by IFITM3. J. Virol. 95 e01994-20.

  • Everitt, A.R., Clare, S., Pertel, T., John, S.P., Wash, R.S., Smith, S.E., Chin, C.R., Feeley, E.M., Sims, J.S., Adams, D.J., Wise, H.M., Kane, L., Goulding, D., Digard, P., Anttila, V., Baillie, J.K., Walsh, T.S., Hume, D.A., Palotie, A., Xue, Y., Colonna, V., Tyler-Smith, C., Dunning, J., Gordon, S.B., Gen, I.I., Investigators, M., Smyth, R.L., Openshaw, P.J., Dougan, G., Brass, A.L., Kellam, P., 2012. IFITM3 restricts the morbidity and mortality associated with influenza. Nature 484, 519-523.

  • Floyd, D.L., Ragains, J.R., Skehel, J.J., Harrison, S.C., Van Oijen, A.M., 2008. Singleparticle kinetics of influenza virus membrane fusion. Proc. Natl. Acad. Sci. U. S. A. 105, 15382-15387.

  • Foster, T., Wilson, H., Iyer, S., Coss, K., Doores, K., Smith, S., Kellam, P., Finzi, A., Borrow, P., Hahn, B., Neil, S., 2016. Resistance of transmitted founder HIV-1 to IFITM-mediated restriction. Cell Host Microbe 20, 429-442.

  • Franz, S., Pott, F., Zillinger, T., Schuler, C., Dapa, S., Fischer, C., Passos, V., Stenzel, S., Chen, F., Dohner, K., Hartmann, G., Sodeik, B., Pessler, F., Simmons, G., Drexler, J.F., Goffinet, C., 2021. Human IFITM3 restricts chikungunya virus and Mayaro virus infection and is susceptible to virus-mediated counteraction. Life Sci Alliance 4, e202000909.

  • Goraya, M.U., Zaighum, F., Sajjad, N., Anjum, F.R., Sakhawat, I., Rahman, S.U., 2020. Web of interferon stimulated antiviral factors to control the influenza A viruses replication. Microb. Pathog. 139, 103919.

  • Guo, X., Steinkuhler, J., Marin, M., Li, X., Lu, W., Dimova, R., Melikyan, G.B., 2021. Interferon-induced transmembrane protein 3 blocks fusion of diverse enveloped viruses by altering mechanical properties of cell membranes. ACS Nano 15, 8155-8170.

  • Hamilton, B.S., Whittaker, G.R., Daniel, S., 2012. Influenza virus-mediated membrane fusion:determinants of hemagglutinin fusogenic activity and experimental approaches for assessing virus fusion. Viruses 4, 1144-1168.

  • Hanagata, N., Li, X., Morita, H., Takemura, T., Li, J., Minowa, T., 2011. Characterization of the osteoblast-specific transmembrane protein IFITM5 and analysis of IFITM5-deficient mice. J. Bone Miner. Metabol. 29, 279-290.

  • Hay, A.J., Gregory, V., Douglas, A.R., Lin, Y.P., 2001. The evolution of human influenza viruses. Philos. Trans. R. Soc. Lond. B Biol. Sci. 356, 1861-1870.

  • Hensen, L., Matrosovich, T., Roth, K., Klenk, H.D., Matrosovich, M., 2019. HA-dependent tropism of H5N1 and H7N9 influenza viruses to human endothelial cells is determined by reduced stability of the HA, which allows the virus to cope with inefficient endosomal acidification and constitutively expressed IFITM3. J. Virol. 94 e01223-19.

  • Huang, D.L., Li, Y., Liang, J., Yu, L., Xue, M., Cao, X.X., Xiao, B., Tian, C.L., Liu, L., Zheng, J.S., 2020. The new salicylaldehyde S,S-propanedithioacetal ester enables Nto-C sequential native chemical ligation and ser/thr ligation for chemical protein synthesis. J. Am. Chem. Soc. 142, 8790-8799.

  • Huang, I.C., Bailey, C.C., Weyer, J.L., Radoshitzky, S.R., Becker, M.M., Chiang, J.J., Brass, A.L., Ahmed, A.A., Chi, X., Dong, L., Longobardi, L.E., Boltz, D., Kuhn, J.H., Elledge, S.J., Bavari, S., Denison, M.R., Choe, H., Farzan, M., 2011. Distinct patterns of IFITM-mediated restriction of filoviruses, SARS coronavirus, and influenza A virus. PLoS Pathog. 7, e1001258.

  • Jia, R., Xu, F., Qian, J., Yao, Y., Miao, C., Zheng, Y.M., Liu, S.L., Guo, F., Geng, Y., Qiao, W., Liang, C., 2014. Identification of an endocytic signal essential for the antiviral action of IFITM3. Cell Microbiol. 16, 1080-1093.

  • John, S., Chin, C., Perreira, J., Feeley, E., Aker, A., Savidis, G., Smith, S., Elia, A., Everitt, A., Vora, M., Pertel, T., Elledge, S., Kellam, P., Brass, A., 2013. The CD225 domain of IFITM3 is required for both IFITM protein association and inhibition of influenza A virus and dengue virus replication. J. Virol. 87, 7837-7852.

  • Kenney, A.D., Mcmichael, T.M., Imas, A., Chesarino, N.M., Zhang, L., Dorn, L.E., Wu, Q., Alfaour, O., Amari, F., Chen, M., Zani, A., Chemudupati, M., Accornero, F., Coppola, V., Rajaram, M.V.S., Yount, J.S., 2019. IFITM3 protects the heart during influenza virus infection. Proc. Natl. Acad. Sci. U. S. A. 116, 18607-18612.

  • Kim, C.S., Epand, R.F., Leikina, E., Epand, R.M., Chernomordik, L.V., 2011. The final conformation of the complete ectodomain of the HA2 subunit of influenza hemagglutinin can by itself drive low pH-dependent fusion. J. Biol. Chem. 286, 13226-13234.

  • Kummer, S., Avinoam, O., Krausslich, H.G., 2019. IFITM3 clusters on virus containing endosomes and lysosomes early in the influenza A infection of human airway epithelial cells. Viruses 11, 548.

  • Lai, A., Freed, J., 2015. The interaction between influenza HA fusion peptide and transmembrane domain affects membrane structure. Biophys. J. 109, 2523-2536.

  • Lanz, C., Schotsaert, M., Magnus, C., Karakus, U., Hunziker, A., Sempere Borau, M., Martinez-Romero, C., Spieler, E.E., Gunther, S.C., Moritz, E., Hale, B.G., Trkola, A., Garcia-Sastre, A., Stertz, S., 2021. IFITM3 incorporation sensitizes influenza A virus to antibody-mediated neutralization. J. Exp. Med. 218, e20200303.

  • Li, Y., Wei, L., He, L., Sun, J., Liu, N., 2022. Interferon-induced transmembrane protein 3 gene polymorphisms are associated with COVID-19 susceptibility and severity:a meta-analysis. J. Infect. 84, 825-833.

  • Lin, T.Y., Chin, C.R., Everitt, A.R., Clare, S., Perreira, J.M., Savidis, G., Aker, A.M., John, S.P., Sarlah, D., Carreira, E.M., Elledge, S.J., Kellam, P., Brass, A.L., 2013. Amphotericin B increases influenza A virus infection by preventing IFITM3-mediated restriction. Cell Rep. 5, 895-908.

  • Majdoul, S., Compton, A.A., 2022. Lessons in self-defence:inhibition of virus entry by intrinsic immunity. Nat. Rev. Immunol. 22, 339-352.

  • Marziali, F., Cimarelli, A., 2021. Membrane interference against HIV-1 by intrinsic antiviral factors:the case of IFITMs. Cells 10, 1171.

  • Mcmichael, T.M., Zhang, L., Chemudupati, M., Hach, J.C., Kenney, A.D., Hang, H.C., Yount, J.S., 2017. The palmitoyltransferase ZDHHC20 enhances interferon-induced transmembrane protein 3 (IFITM3) palmitoylation and antiviral activity. J. Biol. Chem. 292, 21517-21526.

  • Narayana, S., Helbig, K., Mccartney, E., Eyre, N., Bull, R., Eltahla, A., Lloyd, A., Beard, M., 2015. The interferon-induced transmembrane proteins, IFITM1, IFITM2, and IFITM3 inhibit hepatitis C virus entry. J. Biol. Chem. 290, 25946-25959.

  • Nayak, D.P., Hui, E.K., Barman, S., 2004. Assembly and budding of influenza virus. Virus Res. 106, 147-165.

  • Peacock, T.P., Goldhill, D.H., Zhou, J., Baillon, L., Frise, R., Swann, O.C., Kugathasan, R., Penn, R., Brown, J.C., Sanchez-David, R.Y., Braga, L., Williamson, M.K., Hassard, J.A., Staller, E., Hanley, B., Osborn, M., Giacca, M., Davidson, A.D., Matthews, D.A., Barclay, W.S., 2021. The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets. Nat Microbiol 6, 899-909.

  • Prelli Bozzo, C., Nchioua, R., Volcic, M., Koepke, L., Kruger, J., Schutz, D., Heller, S., Sturzel, C.M., Kmiec, D., Conzelmann, C., Muller, J., Zech, F., Braun, E., Gross, R., Wettstein, L., Weil, T., Weiss, J., Diofano, F., Rodriguez Alfonso, A.A., Wiese, S., Sauter, D., Munch, J., Goffinet, C., Catanese, A., Schon, M., Boeckers, T.M., Stenger, S., Sato, K., Just, S., Kleger, A., Sparrer, K.M.J., Kirchhoff, F., 2021. IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro. Nat. Commun. 12, 4584.

  • Rahman, K., Coomer, C.A., Majdoul, S., Ding, S.Y., Padilla-Parra, S., Compton, A.A., 2020. Homology-guided identification of a conserved motif linking the antiviral functions of IFITM3 to its oligomeric state. Elife 9.

  • Rajah, M.M., Hubert, M., Bishop, E., Saunders, N., Robinot, R., Grzelak, L., Planas, D., Dufloo, J., Gellenoncourt, S., Bongers, A., Zivaljic, M., Planchais, C., GuivelBenhassine, F., Porrot, F., Mouquet, H., Chakrabarti, L.A., Buchrieser, J., Schwartz, O., 2021. SARS-CoV-2 Alpha, Beta, and Delta variants display enhanced Spike-mediated syncytia formation. EMBO J. 40, e108944.

  • Ren, L., Du, S., Xu, W., Li, T., Wu, S., Jin, N., Li, C., 2020. Current progress on host antiviral factor IFITMs. Front. Immunol. 11, 543444.

  • Russell, C.J., Hu, M., Okda, F.A., 2018. Influenza hemagglutinin protein stability, activation, and pandemic risk. Trends Microbiol. 26, 841-853.

  • Shi, G., Kenney, A., Kudryashova, E., Zani, A., Zhang, L., Lai, K., Hall-Stoodley, L., Robinson, R., Kudryashov, D., Compton, A., Yount, J., 2021. Opposing activities of IFITM proteins in SARS-CoV-2 infection. EMBO J. 40, e106501.

  • Skehel, J.J., Wiley, D.C., 2000. Receptor binding and membrane fusion in virus entry:the influenza hemagglutinin. Annu. Rev. Biochem. 69, 531-569.

  • Spence, J.S., He, R., Hoffmann, H.H., Das, T., Thinon, E., Rice, C.M., Peng, T., Chandran, K., Hang, H.C., 2019. IFITM3 directly engages and shuttles incoming virus particles to lysosomes. Nat. Chem. Biol. 15, 259-268.

  • Suddala, K.C., Lee, C.C., Meraner, P., Marin, M., Markosyan, R.M., Desai, T.M., Cohen, F.S., Brass, A.L., Melikyan, G.B., 2019. Interferon-induced transmembrane protein 3 blocks fusion of sensitive but not resistant viruses by partitioning into viruscarrying endosomes. PLoS Pathog. 15, e1007532.

  • Sun, F., Xia, Z., Han, Y., Gao, M., Wang, L., Wu, Y., Sabatier, J., Miao, L., Cao, Z., 2020a. Topology, antiviral functional residues and mechanism of IFITM1. Viruses 12, 295.

  • Sun, Q., Lei, N., Lu, J., Gao, R.B., Li, Z., Liu, L.Q., Sun, Y., Guo, J.F., Wang, D.Y., Shu, Y.L., 2020b. Interferon-induced transmembrane protein 3 prevents acute influenza pathogenesis in mice. Biomed. Environ. Sci. 33, 295-305.

  • Tanaka, S.S., Yamaguchi, Y.L., Tsoi, B., Lickert, H., Tam, P.P., 2005. IFITM/Mil/fragilis family proteins IFITM1 and IFITM3 play distinct roles in mouse primordial germ cell homing and repulsion. Dev. Cell 9, 745-756.

  • Tong, S., Zhu, X., Li, Y., Shi, M., Zhang, J., Bourgeois, M., Yang, H., Chen, X., Recuenco, S., Gomez, J., Chen, L.M., Johnson, A., Tao, Y., Dreyfus, C., Yu, W., Mcbride, R., Carney, P.J., Gilbert, A.T., Chang, J., Guo, Z., Davis, C.T., Paulson, J.C., Stevens, J., Rupprecht, C.E., Holmes, E.C., Wilson, I.A., Donis, R.O., 2013. New world bats harbor diverse influenza A viruses. PLoS Pathog. 9, e1003657.

  • Wagner, R., Matrosovich, M., Klenk, H.D., 2002. Functional balance between haemagglutinin and neuraminidase in influenza virus infections. Rev. Med. Virol. 12, 159-166.

  • Warren, C., Griffin, L., Little, A., Huang, I., Farzan, M., Pyeon, D., 2014. The antiviral restriction factors IFITM1, 2 and 3 do not inhibit infection of human papillomavirus, cytomegalovirus and adenovirus. PLoS One 9, e96579.

  • Wellington, D., Laurenson-Schafer, H., Abdel-Haq, A., Dong, T., 2019. IFITM3:how genetics influence influenza infection demographically. Biomed. J. 42, 19-26.

  • Weston, S., Czieso, S., White, I., Smith, S., Kellam, P., Marsh, M., 2014. A membrane topology model for human interferon inducible transmembrane protein 1. PLoS One 9, e104341.

  • Winkler, M., Wrensch, F., Bosch, P., Knoth, M., Schindler, M., Gärtner, S., Pöhlmann, S., 2019. Analysis of IFITM-IFITM interactions by a flow cytometry-based FRET assay.Int. J. Mol. Sci. 20, 3859.

  • Xie, M., Xuan, B., Shan, J., Pan, D., Sun, Y., Shan, Z., Zhang, J., Yu, D., Li, B., Qian, Z., 2015. Human cytomegalovirus exploits interferon-induced transmembrane proteins to facilitate morphogenesis of the virion assembly compartment. J. Virol. 89, 3049-3061.

  • Xu-Yang, Z., Pei-Yu, B., Chuan-Tao, Y., Wei, Y., Hong-Wei, M., Kang, T., Chun-Mei, Z., Ying-Feng, L., Xin, W., Ping-Zhong, W., Chang-Xing, H., Xue-Fan, B., Ying, Z., ZhanSheng, J., 2016. Interferon-induced transmembrane protein 3 inhibits hantaan virus infection, and its single nucleotide polymorphism rs12252 influences the severity of hemorrhagic fever with renal syndrome. Front. Immunol. 7, 535.

  • Yánez, D., Ross, S., Crompton, T., 2020. The IFITM protein family in adaptive immunity. Immunology 159, 365-372.

  • Yount, J., Karssemeijer, R., Hang, H., 2012. S-palmitoylation and ubiquitination differentially regulate interferon-induced transmembrane protein 3 (IFITM3)-mediated resistance to influenza virus. J. Biol. Chem. 287, 19631-19641.

  • Yount, J., Moltedo, B., Yang, Y., Charron, G., Moran, T., López, C., Hang, H., 2010. Palmitoylome profiling reveals S-palmitoylation-dependent antiviral activity of IFITM3. Nat. Chem. Biol. 6, 610-614.

  • Zhang, Y., Makvandi-Nejad, S., Qin, L., Zhao, Y., Zhang, T., Wang, L., Repapi, E., Taylor, S., Mcmichael, A., Li, N., Dong, T., Wu, H., 2015. Interferon-induced transmembrane protein-3 rs12252-C is associated with rapid progression of acute HIV-1 infection in Chinese MSM cohort. AIDS 29, 889-894.

  • Zhang, Y., Qin, L., Zhao, Y., Zhang, P., Xu, B., Li, K., Liang, L., Zhang, C., Dai, Y., Feng, Y., Sun, J., Hu, Z., Xiang, H., Knight, J., Dong, T., Jin, R., 2020. Interferon-induced transmembrane protein 3 genetic variant rs12252-C associated with disease severity in coronavirus disease 2019. J. Infect. Dis. 222, 34-37.

  • Zhao, X., Guo, F., Liu, F., Cuconati, A., Chang, J., Block, T., Guo, J., 2014. Interferon induction of IFITM proteins promotes infection by human coronavirus OC43. Proc. Natl. Acad. Sci. U. S. A. 111, 6756-6761.