Host antiviral factors hijack furin to block SARS-CoV-2, ebola virus, and HIV-1 glycoproteins cleavage

References

• Poranen MM, Daugelavicius R, Bamford DH. Common principles in viral entry. Annu Rev Microbiol. 2002;56:521–538.
   PubMed Web of Science ®Google Scholar
• Plemper RK. Cell entry of enveloped viruses. Curr Opin Virol. 2011 Aug;1(2):92–100.
   PubMed Web of Science ®Google Scholar
• Lu L, Su S, Yang H, et al. Antivirals with common targets against highly pathogenic viruses. Cell. 2021 Mar 18;184(6):1604–1620.
   PubMed Web of Science ®Google Scholar
• Wei W, Yu XF. HIV-1 envelope under attack. Trends Microbiol. 2016 Mar;24(3):164–166.
   PubMed Web of Science ®Google Scholar
• Zhou T, Dang Y, Zheng YH. The mitochondrial translocator protein, TSPO, inhibits HIV-1 envelope glycoprotein biosynthesis via the endoplasmic reticulum-associated protein degradation pathway. J Virol. 2014 Mar;88(6):3474–3484.
   PubMed Web of Science ®Google Scholar
• Usami Y, Wu Y, Gottlinger HG. SERINC3 and SERINC5 restrict HIV-1 infectivity and are counteracted by Nef. Nature. 2015 Oct 8;526(7572):218–223.
   PubMed Web of Science ®Google Scholar
• Rosa A, Chande A, Ziglio S, et al. HIV-1 Nef promotes infection by excluding SERINC5 from virion incorporation. Nature. 2015 Oct 8;526(7572):212–217.
   PubMed Web of Science ®Google Scholar
• Brass AL, Huang IC, Benita Y, et al. The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus. Cell. 2009 Dec 24;139(7):1243–1254.
   PubMed Web of Science ®Google Scholar
• Lodermeyer V, Suhr K, Schrott N, et al. 90 K, an interferon-stimulated gene product, reduces the infectivity of HIV-1. Retrovirology. 2013 Oct 24;10:111.
   PubMed Web of Science ®Google Scholar
• Braun E, Sauter D. Furin-mediated protein processing in infectious diseases and cancer. Clin Transl Immunology. 2019;8(8):e1073.
   PubMed Web of Science ®Google Scholar
• Thomas G. Furin at the cutting edge: from protein traffic to embryogenesis and disease. Nat Rev Mol Cell Biol. 2002 Oct;3(10):753–766.
   PubMed Web of Science ®Google Scholar
• Zhou A, Martin S, Lipkind G, et al. Regulatory roles of the P domain of the subtilisin-like prohormone convertases. J Biol Chem. 1998 May 1;273(18):11107–11114.
   PubMed Web of Science ®Google Scholar
• Braun E, Hotter D, Koepke L, et al. Guanylate-binding proteins 2 and 5 exert broad antiviral activity by inhibiting furin-mediated processing of viral envelope proteins. Cell Rep. 2019 May 14;27(7):2092–104 e10.
   PubMed Web of Science ®Google Scholar
• Yu C, Li S, Zhang X, et al. MARCH8 inhibits ebola virus glycoprotein, human immunodeficiency virus type 1 envelope glycoprotein, and avian influenza virus H5N1 hemagglutinin maturation. mBio. 2020 Sep 15;11(5):e01882–20.
   PubMed Web of Science ®Google Scholar
• Wang J, Luo J, Wen Z, et al. Alpha-soluble NSF attachment protein prevents the cleavage of the SARS-CoV-2 spike protein by functioning as an interferon-upregulated furin inhibitor. mBio. 2022 Jan 11;13(1):e0244321.
   PubMed Web of Science ®Google Scholar
• Kim W, Zekas E, Lodge R, et al. Neuroinflammation-induced interactions between protease-activated receptor 1 and proprotein convertases in HIV-associated neurocognitive disorder. Mol Cell Biol. 2015 Nov;35(21):3684–3700.
   PubMed Web of Science ®Google Scholar
• Zhang R, Li Z, Tang YD, et al. When human guanylate-binding proteins meet viral infections. J Biomed Sci. 2021 Mar 5;28(1):17.
   PubMed Web of Science ®Google Scholar
• Prakash B, Praefcke GJ, Renault L, et al. Structure of human guanylate-binding protein 1 representing a unique class of GTP-binding proteins. Nature. 2000 Feb 3;403(6769):567–571.
   PubMed Web of Science ®Google Scholar
• Modiano N, Lu YE, Cresswell P. Golgi targeting of human guanylate-binding protein-1 requires nucleotide binding, isoprenylation, and an IFN-gamma-inducible cofactor. Proc Natl Acad Sci U S A. 2005 Jun 14;102(24):8680–8685.
   PubMed Web of Science ®Google Scholar
• McLaren PJ, Gawanbacht A, Pyndiah N, et al. Identification of potential HIV restriction factors by combining evolutionary genomic signatures with functional analyses. Retrovirology. 2015 May 16;12:41.
   PubMed Web of Science ®Google Scholar
• Krapp C, Hotter D, Gawanbacht A, et al. Guanylate Binding Protein (GBP) 5 is an interferon-inducible inhibitor of HIV-1 infectivity. Cell Host Microbe. 2016 Apr 13;19(4):504–514.
   PubMed Web of Science ®Google Scholar
• Srinivasachar Badarinarayan S, Shcherbakova I, Langer S, et al. HIV-1 infection activates endogenous retroviral promoters regulating antiviral gene expression. Nucleic Acids Res. 2020 Nov 4;48(19):10890–10908.
   PubMed Web of Science ®Google Scholar
• Hanke K, Kramer P, Seeher S, et al. Reconstitution of the ancestral glycoprotein of human endogenous retrovirus k and modulation of its functional activity by truncation of the cytoplasmic domain. J Virol. 2009 Dec;83(24):12790–12800.
   PubMed Web of Science ®Google Scholar
• Hossain MG, Tang YD, Akter S, et al. Roles of the polybasic furin cleavage site of spike protein in SARS-CoV-2 replication, pathogenesis, and host immune responses and vaccination. J Med Virol. 2022 May;94(5):1815–1820.
   PubMed Web of Science ®Google Scholar
• Papa G, Mallery DL, Albecka A, et al. Furin cleavage of SARS-CoV-2 spike promotes but is not essential for infection and cell-cell fusion. PLoS Pathog. 2021 Jan;17(1):e1009246.
   PubMed Web of Science ®Google Scholar
• Peacock TP, Goldhill DH, Zhou J, et al. The furin cleavage site in the SARS-CoV-2 spike protein is required for transmission in ferrets. Nat Microbiol. 2021 Jul;6(7):899–909.
   PubMed Web of Science ®Google Scholar
• Cui W, Braun E, Wang W, et al. Structural basis for GTP-induced dimerization and antiviral function of guanylate-binding proteins. Proc Natl Acad Sci U S A. 2021 Apr 13;118(15):e2022269118.
   PubMed Web of Science ®Google Scholar
• Bartee E, Mansouri M, Hovey Nerenberg BT, et al. Downregulation of major histocompatibility complex class I by human ubiquitin ligases related to viral immune evasion proteins. J Virol. 2004 Feb;78(3):1109–1120.
   PubMed Web of Science ®Google Scholar
• Tada T, Zhang Y, Fujita H, et al. MARCH8: the tie that binds to viruses. FEBS J. 2022 Jul;289(13):3642–3654.
   PubMed Web of Science ®Google Scholar
• Lin H, Li S, Shu HB. The membrane-associated MARCH E3 ligase family: emerging roles in immune regulation. Front Immunol. 2019;10:1751.
   PubMed Web of Science ®Google Scholar
• Zheng C. The emerging roles of the MARCH ligases in antiviral innate immunity. Int J Biol Macromol. 2021 Feb 28;171:423–427.
   PubMed Web of Science ®Google Scholar
• Yang X, Shi C, Li H, et al. MARCH8 attenuates cGAS-mediated innate immune responses through ubiquitylation. Sci Signal. 2022 May 3;15(732):eabk3067.
   PubMed Web of Science ®Google Scholar
• Jin S, Cui J. BST2 inhibits type I IFN (interferon) signaling by accelerating MAVS degradation through CALCOCO2-directed autophagy. Autophagy. 2018;14(1):171–172.
   PubMed Web of Science ®Google Scholar
• Tada T, Zhang Y, Koyama T, et al. MARCH8 inhibits HIV-1 infection by reducing virion incorporation of envelope glycoproteins. Nat Med. 2015 Dec;21(12):1502–1507.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Tada T, Ozono S, et al. Membrane-associated RING-CH (MARCH) 1 and 2 are MARCH family members that inhibit HIV-1 infection. J Biol Chem. 2019 Mar 8;294(10):3397–3405.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Lu J, Liu X. MARCH2 is upregulated in HIV-1 infection and inhibits HIV-1 production through envelope protein translocation or degradation. Virology. 2018 May;518:293–300.
   PubMed Web of Science ®Google Scholar
• Zheng C, Tang YD. When MARCH family proteins meet viral infections. Virol J. 2021 Mar 2;18(1):49.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Tada T, Ozono S, et al. MARCH8 inhibits viral infection by two different mechanisms. Elife. 2020 Aug 11;9:e57763.
   PubMed Web of Science ®Google Scholar
• Lun CM, Waheed AA, Majadly A, et al. Mechanism of viral glycoprotein targeting by membrane-associated RING-CH proteins. mBio. 2021 Mar 16;12(2):e00219–21.
   PubMed Web of Science ®Google Scholar
• Umthong S, Lynch B, Timilsina U, et al. Elucidating the antiviral mechanism of different MARCH factors. mBio. 2021 Mar 2;12(2):e03264–20.
   PubMed Web of Science ®Google Scholar
• Liu X, Xu F, Ren L, et al. MARCH8 inhibits influenza A virus infection by targeting viral M2 protein for ubiquitination-dependent degradation in lysosomes. Nat Commun. 2021 Jul 20;12(1):4427.
   PubMed Web of Science ®Google Scholar
• Villalon-Letelier F, Brooks AG, Londrigan SL, et al. MARCH8 restricts influenza A virus infectivity but does Not downregulate viral glycoprotein expression at the surface of infected cells. mBio. 2021 Oct 26;12(5):e0148421.
   PubMed Web of Science ®Google Scholar
• Villalon-Letelier F, Farrukee R, Londrigan SL, et al. Isoforms of human MARCH1 differ in ability to restrict influenza A viruses due to differences in their N terminal cytoplasmic domain. Viruses. 2022 Nov 18;14(11):v14112549.
   Web of Science ®Google Scholar
• Li C, Shi L, Gao Y, et al. HSC70 inhibits spring viremia of carp virus replication by inducing MARCH8-mediated lysosomal degradation of G protein. Front Immunol. 2021;12:724403.
   PubMed Web of Science ®Google Scholar
• Zhang Y, Ozono S, Tada T, et al. MARCH8 targets cytoplasmic lysine residues of various viral envelope glycoproteins. Microbiol Spectr. 2022 Feb 23;10(1):e0061821.
   PubMed Web of Science ®Google Scholar
• Nakamura N, Fukuda H, Kato A, et al. MARCH-II is a syntaxin-6-binding protein involved in endosomal trafficking. Mol Biol Cell. 2005 Apr;16(4):1696–1710.
   PubMed Web of Science ®Google Scholar
• Andreeva AV, Kutuzov MA, Voyno-Yasenetskaya TA. A ubiquitous membrane fusion protein alpha SNAP: a potential therapeutic target for cancer, diabetes and neurological disorders? Expert Opin Ther Targets. 2006 Oct;10(5):723–733.
   PubMed Web of Science ®Google Scholar
• Whiteheart SW, Griff IC, Brunner M, et al. SNAP family of NSF attachment proteins includes a brain-specific isoform. Nature. 1993 Mar 25;362(6418):353–355.
   PubMed Web of Science ®Google Scholar
• Furst J, Sutton RB, Chen J, et al. Electron cryomicroscopy structure of N-ethyl maleimide sensitive factor at 11 A resolution. EMBO J. 2003 Sep 1;22(17):4365–4374.
   PubMed Web of Science ®Google Scholar
• Zhou Q, Huang X, Sun S, et al. Cryo-EM structure of SNAP-SNARE assembly in 20S particle. Cell Res. 2015 May;25(5):551–560.
   PubMed Web of Science ®Google Scholar
• Zhao C, Slevin JT, Whiteheart SW. Cellular functions of NSF: not just SNAPs and SNAREs. FEBS Lett. 2007 May 22;581(11):2140–2149.
   PubMed Web of Science ®Google Scholar
• Jahn R, Lang T, Sudhof TC. Membrane fusion. Cell. 2003 Feb 21;112(4):519–533.
   PubMed Web of Science ®Google Scholar
• Han X, Nieman MT, Kerlin BA. Protease-activated receptors: an illustrated review. Res Pract Thromb Haemost. 2021 Jan;5(1):17–26.
   PubMed Web of Science ®Google Scholar
• Chandrabalan A, Ramachandran R. Molecular mechanisms regulating proteinase-activated receptors (PARs). FEBS J. 2021 Apr;288(8):2697–2726.
   PubMed Web of Science ®Google Scholar
• Adams MN, Ramachandran R, Yau MK, et al. Structure, function and pathophysiology of protease activated receptors. Pharmacol Ther. 2011 Jun;130(3):248–282.
   PubMed Web of Science ®Google Scholar
• Aerts L, Hamelin ME, Rheaume C, et al. Modulation of protease activated receptor 1 influences human metapneumovirus disease severity in a mouse model. PLoS One. 2013;8(8):e72529.
   PubMed Web of Science ®Google Scholar
• Sachan V, Lodge R, Mihara K, et al. HIV-induced neuroinflammation: impact of PAR1 and PAR2 processing by Furin. Cell Death Differ. 2019 Oct;26(10):1942–1954.
   PubMed Web of Science ®Google Scholar
• Capone E, Iacobelli S, Sala G. Role of galectin 3 binding protein in cancer progression: a potential novel therapeutic target. J Transl Med. 2021 Sep 26;19(1):405.
   PubMed Web of Science ®Google Scholar
• Iacobelli S, Natoli C, D'Egidio M, et al. Lipoprotein 90 K in human immunodeficiency virus-infected patients: a further serologic marker of progression. J Infect Dis. 1991 Oct;164(4):819.
   PubMed Web of Science ®Google Scholar
• Xu G, Xia Z, Deng F, et al. Inducible LGALS3BP/90 K activates antiviral innate immune responses by targeting TRAF6 and TRAF3 complex. PLoS Pathog. 2019 Aug;15(8):e1008002.
   PubMed Web of Science ®Google Scholar
• Lodermeyer V, Ssebyatika G, Passos V, et al. The antiviral activity of the cellular glycoprotein LGALS3BP/90 K Is species specific. J Virol. 2018 Jul 15;92(14):e00226–18.
   PubMed Web of Science ®Google Scholar
• Wang Q, Zhang X, Han Y, et al. M2BP inhibits HIV-1 virion production in a vimentin filaments-dependent manner. Sci Rep. 2016 Sep 8;6:32736.
   PubMed Web of Science ®Google Scholar
• Gutmann C, Takov K, Burnap SA, et al. SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care. Nat Commun. 2021 Jun 7;12(1):3406.
   PubMed Web of Science ®Google Scholar
• Zhao X, Li J, Winkler CA, et al. IFITM genes, variants, and their roles in the control and pathogenesis of viral infections. Front Microbiol. 2018;9:3228.
   PubMed Web of Science ®Google Scholar
• Yanez DC, Ross S, Crompton T. The IFITM protein family in adaptive immunity. Immunology. 2020 Apr;159(4):365–372.
   PubMed Web of Science ®Google Scholar
• Bailey CC, Zhong G, Huang IC, et al. IFITM-family proteins: the cell's first line of antiviral defense. Annu Rev Virol. 2014 Nov 1;1:261–283.
   PubMed Web of Science ®Google Scholar
• Savidis G, Perreira JM, Portmann JM, et al. The IFITMs inhibit Zika virus replication. Cell Rep. 2016 Jun 14;15(11):2323–2330.
   PubMed Web of Science ®Google Scholar
• Shi G, Kenney AD, Kudryashova E, et al. Opposing activities of IFITM proteins in SARS-CoV-2 infection. EMBO J. 2021 Feb 1;40(3):e106501.
   PubMed Web of Science ®Google Scholar
• Compton AA, Bruel T, Porrot F, et al. IFITM proteins incorporated into HIV-1 virions impair viral fusion and spread. Cell Host Microbe. 2014 Dec 10;16(6):736–747.
   PubMed Web of Science ®Google Scholar
• Yu J, Li M, Wilkins J, et al. IFITM proteins restrict HIV-1 infection by antagonizing the envelope glycoprotein. Cell Rep. 2015 Oct 6;13(1):145–156.
   PubMed Web of Science ®Google Scholar
• Prelli Bozzo C, Nchioua R, Volcic M, et al. IFITM proteins promote SARS-CoV-2 infection and are targets for virus inhibition in vitro. Nat Commun. 2021 Jul 28;12(1):4584.
   PubMed Web of Science ®Google Scholar
• Nchioua R, Schundner A, Kmiec D, et al. SARS-CoV-2 variants of concern hijack IFITM2 for efficient replication in human lung cells. J Virol. 2022 Jun 8;96(11):e0059422.
   PubMed Web of Science ®Google Scholar
• Hallenberger S, Bosch V, Angliker H, et al. Inhibition of furin-mediated cleavage activation of HIV-1 glycoprotein gp160. Nature. 1992 Nov 26;360(6402):358–361.
   PubMed Web of Science ®Google Scholar
• Imran M, Saleemi MK, Chen Z, et al. Decanoyl-Arg-Val-Lys-Arg-Chloromethylketone: an antiviral compound that acts against flaviviruses through the inhibition of furin-mediated prM cleavage. Viruses. 2019 Oct 31;11(11):v11111011.
   Web of Science ®Google Scholar
• Cheng YW, Chao TL, Li CL, et al. Furin inhibitors block SARS-CoV-2 spike protein cleavage to suppress virus production and cytopathic effects. Cell Rep. 2020 Oct 13;33(2):108254.
   PubMed Web of Science ®Google Scholar
• Hardes K, Becker GL, Lu Y, et al. Novel furin inhibitors with potent anti-infectious activity. ChemMedChem. 2015 Jul;10(7):1218–1231.
   PubMed Web of Science ®Google Scholar
• Kouretova J, Hammamy MZ, Epp A, et al. Effects of NS2B-NS3 protease and furin inhibition on West Nile and dengue virus replication. J Enzyme Inhib Med Chem. 2017 Dec;32(1):712–721.
   PubMed Web of Science ®Google Scholar
• Kuivanen S, Bespalov MM, Nandania J, et al. Obatoclax, saliphenylhalamide and gemcitabine inhibit Zika virus infection in vitro and differentially affect cellular signaling, transcription and metabolism. Antiviral Res. 2017 Mar;139:117–128.
   PubMed Web of Science ®Google Scholar
• Andersen PI, Krpina K, Ianevski A, et al. Novel antiviral activities of obatoclax, emetine, niclosamide, brequinar, and homoharringtonine. Viruses. 2019 Oct 18;11(10):v11100964.
   Web of Science ®Google Scholar
• Mao B, Le-Trilling VTK, Wang K, et al. Obatoclax inhibits SARS-CoV-2 entry by altered endosomal acidification and impaired cathepsin and furin activity in vitro. Emerg Microbes Infect. 2022 Dec;11(1):483–497.
   PubMed Web of Science ®Google Scholar
• del Real G, Jimenez-Baranda S, Mira E, et al. Statins inhibit HIV-1 infection by down-regulating Rho activity. J Exp Med. 2004 Aug 16;200(4):541–547.
   PubMed Web of Science ®Google Scholar
• Shrivastava-Ranjan P, Flint M, Bergeron E, et al. Statins suppress ebola virus infectivity by interfering with glycoprotein processing. mBio. 2018 May 1;9(3):e00660–18.
   PubMed Web of Science ®Google Scholar
• Ahi YS, Yimer D, Shi G, et al. IFITM3 reduces retroviral envelope abundance and function and Is counteracted by glycoGag. mBio. 2020 Jan 21:e03088–19.
   PubMed Web of Science ®Google Scholar