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. 2013 Jul 10;790:83–94. doi: 10.1007/978-1-4614-7651-1_5

Filovirus Entry

Graham Simmons 4
Editors: Stefan Pöhlmann1,2, Graham Simmons3
PMCID: PMC7114988  PMID: 23884587

Abstract

A number of advances in recent years have significantly furthered our understanding of filovirus attachment and cellular tropism. For example, several cell-surface molecules have been identified as attachment factors with the potential to facilitate the in vivo targeting of particular cell types such as macrophages and hepatic cells. Furthermore, our knowledge of internalization and subsequent events during filovirus entry has also been widened, adding new variations to the paradigms for viral entry established for HIV and influenza. In particular, host cell factors such as endosomal proteases and the intracellular receptor Niemann-Pick C1 are now known to play a vital role in activating the membrane fusion potential of filovirus glycoproteins.

Keywords: Membrane Fusion, Marburg Virus, Severe Acute Respiratory Syndrome Coronavirus, Viral Fusion Protein, Folate Receptor Alpha

References

  • 1.Leroy E.M., Gonzalez J.-P., Baize S. Ebola and Marburg haemorrhagic fever viruses: major scientific advances, but a relatively minor public health threat for Africa. Clin Microbiol Infect. 2011;17:964–976. doi: 10.1111/j.1469-0691.2011.03535.x. [DOI] [PubMed] [Google Scholar]
  • 2.Leroy E.M., Kumulungui B., Pourrut X., et al. Fruit bats as reservoirs of Ebola virus. Nature. 2005;438:575–576. doi: 10.1038/438575a. [DOI] [PubMed] [Google Scholar]
  • 3.Towner J.S., Amman B.R., Sealy T.K., et al. Isolation of genetically diverse Marburg viruses from Egyptian fruit bats. PLoS Pathog. 2009;5:e1000536. doi: 10.1371/journal.ppat.1000536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Barrette R.W., Metwally S.A., Rowland J.M., et al. Discovery of swine as a host for the reston Ebola virus. Science. 2009;325:204–206. doi: 10.1126/science.1172705. [DOI] [PubMed] [Google Scholar]
  • 5.Volchkov V.E., Becker S., Volchkova V.A., et al. GP mRNA of Ebola virus is edited by the Ebola virus polymerase and by T7 and vaccinia virus polymerases. Virology. 1995;214:421–430. doi: 10.1006/viro.1995.0052. [DOI] [PubMed] [Google Scholar]
  • 6.Sanchez A., Ksiazek T.G., Rollin P.E., et al. Detection and molecular characterization of Ebola viruses causing disease in human and nonhuman primates. J Infect Dis. 1999;179(Suppl 1):S164–169. doi: 10.1086/514282. [DOI] [PubMed] [Google Scholar]
  • 7.Volchkov V.E., Volchkova V.A., Muhlberger E., et al. Recovery of infectious Ebola virus from complementary DNA: RNA editing of the GP gene and viral cytotoxicity. Science. 2001;291:1965–1969. doi: 10.1126/science.1057269. [DOI] [PubMed] [Google Scholar]
  • 8.Yang Z.Y., Duckers H.J., Sullivan N.J., et al. Identification of the Ebola virus glycoprotein as the main viral determinant of vascular cell cytotoxicity and injury. Nat Med. 2000;6:886–889. doi: 10.1038/78645. [DOI] [PubMed] [Google Scholar]
  • 9.Simmons G., Wool-Lewis R.J., Baribaud F., et al. Ebola virus glycoproteins induce global surface protein down-modulation and loss of cell adherence. J Viro. 2002;76:2518–2528. doi: 10.1128/jvi.76.5.2518-2528.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Marzi A., Wegele A., Pohlmann S. Modulation of virion incorporation of Ebolavirus glycoprotein: Effects on attachment, cellular entry and neutralization. Virology. 2006;352:345–56. doi: 10.1016/j.virol.2006.04.038. [DOI] [PubMed] [Google Scholar]
  • 11.Volchkov V.E., Feldmann H., Volchkova V.A., et al. Processing of the Ebola virus glycoprotein by the proprotein convertase furin. Proc Natl Acad Sci USA. 1998;95:5762–5767. doi: 10.1073/pnas.95.10.5762. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Volchkov V.E., Volchkova V.A., Stroher U., et al. Proteolytic processing of Marburg virus glycoprotein. Virology. 2000;268:1–6. doi: 10.1006/viro.1999.0110. [DOI] [PubMed] [Google Scholar]
  • 13.Jeffers S.A., Sanders D.A., Sanchez A. Covalent modifications of the ebola virus glycoprotein. J Virol. 2002;76:12463–12472. doi: 10.1128/JVI.76.24.12463-12472.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14.Klenk H.D., Garten W. Host cell proteases controlling virus pathogenicity. Trends Microbiol. 1994;2:39–43. doi: 10.1016/0966-842X(94)90123-6. [DOI] [PubMed] [Google Scholar]
  • 15.Wool-Lewis R.J., Bates P. Endoproteolytic processing of the ebola virus envelope glycoprotein: cleavage is not required for function. J Virol. 1999;73:1419–1426. doi: 10.1128/jvi.73.2.1419-1426.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Neumann G., Geisbert T.W., Ebihara H., et al. Proteolytic processing of the Ebola virus glycoprotein is not critical for Ebola virus replication in nonhuman primates. J Virol. 2007;81:2995–2998. doi: 10.1128/JVI.02486-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.Weissenhorn W., Carfi A., Lee K.H., et al. Crystal structure of the Ebola virus membrane fusion subunit, GP2, from the envelope glycoprotein ectodomain. Mol Cell. 1998;2:605–616. doi: 10.1016/S1097-2765(00)80159-8. [DOI] [PubMed] [Google Scholar]
  • 18.White J.M., Delos S.E., Brecher M., Schornberg K. Structures and mechanisms of viral membrane fusion proteins. Crit Rev Biochem Mol Biol. 2008;43(3):189–219. doi: 10.1080/10409230802058320. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Geyer H., Will C., Feldmann H., et al. Carbohydrate structure of Marburg virus glycoprotein. Glycobiology. 1992;2:299–312. doi: 10.1093/glycob/2.4.299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 20.Lee J.E., Fusco M.L., Hessell A.J., et al. Structure of the ebola virus glycoprotein bound to an antibody from a human survivor. Nature. 2008;454:177–182. doi: 10.1038/nature07082. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Sinn P.L., Hickey M.A., Staber P.D., et al. Lentivirus vectors pseudotyped with filoviral envelope glycoproteins transduce airway epithelia from the apical surface independently of folate receptor alpha. J Virol. 2003;77:5902–5910. doi: 10.1128/JVI.77.10.5902-5910.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Manicassamy B., Wang J., Jiang H., et al. Comprehensive analysis of ebola virus GP1 in viral entry. J Virol. 2005;79:4793–4805. doi: 10.1128/JVI.79.8.4793-4805.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Kuhn J.H., Radoshitzky S.R., Guth A.C., et al. Conserved receptor-binding domains of Lake Victoria marburgvirus and Zaire ebolavirus bind a common receptor. J Biol Chem. 2006;281:15951–15958. doi: 10.1074/jbc.M601796200. [DOI] [PubMed] [Google Scholar]
  • 24.Mpanju O.M., Towner J.S., Dover J.E., et al. Identification of two amino acid residues on Ebola virus glycoprotein 1 critical for cell entry. Virus Res. 2006;121:205–14. doi: 10.1016/j.virusres.2006.06.002. [DOI] [PubMed] [Google Scholar]
  • 25.Takada A., Robison C., Goto H., et al. A system for functional analysis of Ebola virus glycoprotein. Proc Natl Acad Sci USA. 1997;94:14764–14769. doi: 10.1073/pnas.94.26.14764. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Wool-Lewis R.J., Bates P. Characterization of Ebola virus entry by usingpseudotyped viruses: identification of receptor-deficient cell lines. J Virol. 1998;72:3155–3160. doi: 10.1128/jvi.72.4.3155-3160.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Chan S.Y., Speck R.F., Ma M.C., et al. Distinct mechanisms of entry by envelope glycoproteins of Marburg and Ebola (Zaire) viruses. J Virol. 2000;74:4933–4937. doi: 10.1128/JVI.74.10.4933-4937.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Ito H., Watanabe S., Takada A., et al. Ebola Virus Glycoprotein: Proteolytic Processing, Acylation, Cell Tropism, and Detection of Neutralizing Antibodies. J Virol. 2001;75:1576–1580. doi: 10.1128/JVI.75.3.1576-1580.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Geisbert T.W., Hensley L.E., Gibb T.R., et al. Apoptosis induced in vitro and in vivo during infection by Ebola and Marburg viruses. Lab Invest. 2000;80:171–186. doi: 10.1038/labinvest.3780021. [DOI] [PubMed] [Google Scholar]
  • 30.Schnittler H.J., Feldmann H. Molecular pathogenesis of filovirus infections: role of macrophages and endothelial cells. Curr Top Microbiol Immunol. 1999;235:175–204. doi: 10.1007/978-3-642-59949-1_10. [DOI] [PubMed] [Google Scholar]
  • 31.Schnittler H.J., Feldmann H. Marburg and Ebola hemorrhagic fevers: does the primary course of infection depend on the accessibility of organ-specific macrophages? Clin Infect Dis. 1998;27:404–406. doi: 10.1086/517704. [DOI] [PubMed] [Google Scholar]
  • 32.Stroher U., West E., Bugany H., et al. Infection and activation of monocytes by Marburg and Ebola viruses. J Virol. 2001;75:11025–11033. doi: 10.1128/JVI.75.22.11025-11033.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 33.Yonezawa A., Cavrois M., Greene W.C. Studies of ebola virus glycoprotein-mediated entry and fusion by using pseudotyped human immunodeficiency virus type 1 virions: involvement of cytoskeletal proteins and enhancement by tumor necrosis factor alpha. J Virol. 2005;79:918–926. doi: 10.1128/JVI.79.2.918-926.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Bosio C.M., Aman M.J., Grogan C., et al. Ebola and Marburg viruses replicate in monocyte-derived dendritic cells without inducing the production of cytokines and full maturation. J Infect Dis. 2003;188:1630–1638. doi: 10.1086/379199. [DOI] [PubMed] [Google Scholar]
  • 35.Kondratowicz A.S., Lennemann N.J., Sinn P.L., et al. T-cell immunoglobulin and mucin domain 1 (tim-1) is a receptor for zaire ebolavirus and lake victoria marburgvirus. Proc Natl Acad Sci USA. 2011;108:8426–8431. doi: 10.1073/pnas.1019030108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 36.Shimojima M., Takada A., Ebihara H., et al. Tyro3 family-mediated cell entry of Ebola and Marburg viruses. J Virol. 2006;80:10109–10116. doi: 10.1128/JVI.01157-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.Brindley M.A., Hunt C.L., Kondratowicz A.S., et al. Tyrosine kinase receptor axl enhances entry of zaire ebolavirus without direct interactions with the viral glycoprotein. Virology. 2011;415:83–94. doi: 10.1016/j.virol.2011.04.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Chan S.Y., Empig C.J., Weite F.J., et al. Folate receptor-alpha is a cofactor for cellular entry by Marburg and Ebola viruses. Cell. 2001;106:117–126. doi: 10.1016/S0092-8674(01)00418-4. [DOI] [PubMed] [Google Scholar]
  • 39.Simmons G., Rennekamp A.J., Chai N., et al. Folate receptor alpha and caveolae are not required for Ebola virus glycoprotein-mediated viral infection. J Virol. 2003;77:13433–13438. doi: 10.1128/JVI.77.24.13433-13438.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 40.Takada A., Watanabe S., Ito H., et al. Downregulation of betal integrins by Ebola virus glycoprotein: implication for virus entry. Virology. 2000;278:20–26. doi: 10.1006/viro.2000.0601. [DOI] [PubMed] [Google Scholar]
  • 41.ODoherty U., Swiggard W.J., Malim M.H. Human immunodeficiency virus type 1 spinoculation enhances infection through virus binding. J Virol. 2000;74:10074–10080. doi: 10.1128/JVI.74.21.10074-10080.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 42.Soilleux E.J., Barten R., Trowsdale J. DC-SIGN; a related gene, DC-SIGNR; and CD23 form a cluster on 19p13. J Immunol. 2000;165:2937–2942. doi: 10.4049/jimmunol.165.6.2937. [DOI] [PubMed] [Google Scholar]
  • 43.Liu W., Tang L., Zhang G., et al. Characterization of a novel C-type lectin-like gene, LSECtin: demonstration of carbohydrate binding and expression in sinusoidal endothelial cells of liver and lymph node. J Biol Chem. 2004;279:18748–18758. doi: 10.1074/jbc.M311227200. [DOI] [PubMed] [Google Scholar]
  • 44.Geijtenbeek T.B., Krooshoop D.J., Bleijs D.A., et al. DC-SIGN-ICAM-2 interaction mediates dendritic cell trafficking. Nat Immunol. 2000;1:353–357. doi: 10.1038/79815. [DOI] [PubMed] [Google Scholar]
  • 45.Geijtenbeek T.B., Torensma R., van Vliet S.J., et al. Identification of DC-SIGN, a novel dendritic cell-specific ICAM-3 receptor that supports primary immune responses. Cell. 2000;100:575–585. doi: 10.1016/S0092-8674(00)80693-5. [DOI] [PubMed] [Google Scholar]
  • 46.Curtis B.M., Scharnowske S., Watson A.J. Sequence and expression of a membrane-associated C-type lectin that exhibits CD4-independent binding of human immunodeficiency virus envelope glycoprotein gp120. Proc Natl Acad Sci USA. 1992;89:8356–8360. doi: 10.1073/pnas.89.17.8356. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 47.Geijtenbeek T.B., Kwon D.S., Torensma R., et al. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that enhances trans-infection of T cells. Cell. 2000;100:587–597. doi: 10.1016/S0092-8674(00)80694-7. [DOI] [PubMed] [Google Scholar]
  • 48.Pohlmann S., Zhang J., Baribaud F., et al. Hepatitis C virus glycoproteins interact with DC-SIGN and DC-SIGNR. J Virol. 2003;77:4070–4080. doi: 10.1128/JVI.77.7.4070-4080.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Tassaneetrithep B., Burgess T.H., Granelli-Piperno A., et al. DC-SIGN (CD209) mediates dengue virus infection of human dendritic cells. J Exp Med. 2003;197:823–829. doi: 10.1084/jem.20021840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 50.Colmenares M., Puig-Kroger A., Pello O.M., et al. Dendritic cell (DC)-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin (DC-SIGN, CD209), a C-type surface lectin in human DCs, is a receptor for Leishmania amastigotes. J Biol Chem. 2002;277:36766–36769. doi: 10.1074/jbc.M205270200. [DOI] [PubMed] [Google Scholar]
  • 51.Geijtenbeek T.B., Van Vliet S.J., Koppel E.A., et al. Mycobacteria target DC-SIGN to suppress dendritic cell function. J Exp Med. 2003;197:7–17. doi: 10.1084/jem.20021229. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Tailleux L., Schwartz O., Herrmann J.L., et al. DC-SIGN is the major Mycobacterium tuberculosis receptor on human dendritic cells. J Exp Med. 2003;197:121–127. doi: 10.1084/jem.20021468. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 53.Simmons G., Reeves J.D., Grogan C.C., et al. DC-SIGN and DC-SIGNR bind ebola glycoproteins and enhance infection of macrophages and endothelial cells. Virology. 2003;305:115–123. doi: 10.1006/viro.2002.1730. [DOI] [PubMed] [Google Scholar]
  • 54.Kaushal G.P., Elbein A.D. Glycosidase inhibitors in study of glycoconjugates. Methods Enzymol. 1994;230:316–329. doi: 10.1016/0076-6879(94)30021-6. [DOI] [PubMed] [Google Scholar]
  • 55.Lin G., Simmons G., Pohlmann S., et al. Differential N-linked glycosylation of human immunodeficiency virus and Ebola virus envelope glycoproteins modulates interactions with DC-SIGN and DC-SIGNR. J Virol. 2003;77:1337–1346. doi: 10.1128/JVI.77.2.1337-1346.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Mitchell D.A., Fadden A.J., Drickamer K. A novel mechanism of carbohydrate recognition by the C-type lectins DC-SIGN and DC-SIGNR. Subunit organization and binding to multivalent ligands. J Biol Chem. 2001;276:28939–28945. doi: 10.1074/jbc.M104565200. [DOI] [PubMed] [Google Scholar]
  • 57.Davis C.W., Nguyen H.Y., Hanna S.L., et al. West Nile virus discriminates between DC-SIGN and DC-SIGNR for cellular attachment and infection. J Virol. 2006;80:1290–1301. doi: 10.1128/JVI.80.3.1290-1301.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 58.Feldmann H., Nichol S.T., Klenk H.D., et al. Characterization of filoviruses based on differences in structure and antigenicity of the virion glycoprotein. Virology. 1994;199:469–473. doi: 10.1006/viro.1994.1147. [DOI] [PubMed] [Google Scholar]
  • 59.Powlesland A.S., Fisch T., Taylor M.E., et al. A novel mechanism for LSECtin binding to Ebola virus surface glycoprotein through truncated glycans. J Biol Chem. 2008;283(1):593–602. doi: 10.1074/jbc.M706292200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 60.Alvarez C.P., Lasala F., Carrillo J., et al. C-type lectins DC-SIGN and L-SIGN mediate cellular entry by Ebola virus in cis and in trans. J Virol. 2002;76:6841–6844. doi: 10.1128/JVI.76.13.6841-6844.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 61.Marzi A., Gramberg T., Simmons G., et al. DC-SIGN and DC-SIGNR interact with the glycoprotein of Marburg virus and the S protein of severe acute respiratory syndrome coronavirus. J Virol. 2004;78:12090–12095. doi: 10.1128/JVI.78.21.12090-12095.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62.Gramberg T., Hofmann H., Moller P., et al. LSECtin interacts with filovirus glycoproteins and the spike protein of SARS coronavirus. Virology. 2005;340:224–36. doi: 10.1016/j.virol.2005.06.026. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63.Soilleux E.J., Morris L.S., Leslie G., et al. Constitutive and induced expression of DC-SIGN on dendritic cell and macrophage subpopulations in situ and in vitro. J Leukoc Biol. 2002;71:445–457. [PubMed] [Google Scholar]
  • 64.Soilleux E.J., Morris L.S., Lee B., et al. Placental expression of DC-SIGN may mediate intrauterine vertical transmission of HIV. J Pathol. 2001;195:586–592. doi: 10.1002/path.1026. [DOI] [PubMed] [Google Scholar]
  • 65.McCully M.L., Chau T.A., Luke P., et al. Characterization of human peritoneal dendritic cell precursors and their involvement in peritonitis. Clin Exp Immunol. 2005;139:513–525. doi: 10.1111/j.1365-2249.2005.02713.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 66.Lai W.K., Sun P.J., Zhang J., et al. Expression of DC-SIGN and DC-SIGNR on human sinusoidal endothelium: a role for capturing hepatitis C virus particles. Am J Pathol. 2006;169:200–208. doi: 10.2353/ajpath.2006.051191. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 67.Bashirova A.A., Geijtenbeek T.B., van Duijnhoven G.C., et al. A dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin (DC-SIGN)-related protein is highly expressed on human liver sinusoidal endothelial cells and promotes HIV-1 infection. J Exp Med. 2001;193:671–678. doi: 10.1084/jem.193.6.671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 68.Becker S., Spiess M., Klenk H.D. The asialoglycoprotein receptor is a potential liver-specific receptor for Marburg virus. J Gen Virol. 1995;76:393–399. doi: 10.1099/0022-1317-76-2-393. [DOI] [PubMed] [Google Scholar]
  • 69.Meier M., Bider M.D., Malashkevich V.N., et al. Crystal structure of the carbohydrate recognition domain of the H1 subunit of the asialoglycoprotein receptor. J Mol Biol. 2000;300:857–865. doi: 10.1006/jmbi.2000.3853. [DOI] [PubMed] [Google Scholar]
  • 70.Takada A., Fujioka K., Tsuiji M., et al. Human macrophage C-type lectin specific for galactose and N-acetylgalactosamine promotes filovirus entry. J Virol. 2004;78:2943–2947. doi: 10.1128/JVI.78.6.2943-2947.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 71.Sieczkarski S.B., Whittaker G.R. Dissecting virus entry via endocytosis. J Gen Virol. 2002;83:1535–1545. doi: 10.1099/0022-1317-83-7-1535. [DOI] [PubMed] [Google Scholar]
  • 72.Empig C.J., Goldsmith M.A. Association of the caveola vesicular system with cellular entry by filoviruses. J Virol. 2002;76:5266–5270. doi: 10.1128/JVI.76.10.5266-5270.2002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 73.Bavari S., Bosio C.M., Wiegand E., et al. Lipid raft microdomains: a gateway for compartmentalized trafficking of Ebola and Marburg viruses. J Exp Med. 2002;195:593–602. doi: 10.1084/jem.20011500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 74.Bhattacharyya S., Warfield K.L., Ruthel G., et al. Ebola virus uses clathrin-mediated endocytosis as an entry pathway. Virology. 2010;401:18–28. doi: 10.1016/j.virol.2010.02.015. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 75.Saeed M.F., Kolokoltsov A.A., Albrecht T., et al. Cellular entry of ebola virus involves uptake by a macropinocytosis-like mechanism and subsequent trafficking through early and late endosomes. PLoS Pathog. 2010;6:e1001110. doi: 10.1371/journal.ppat.1001110. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 76.Nanbo A., Imai M., Watanabe S., et al. Ebolavirus is internalized into host cells via macropinocytosis in a viral glycoprotein-dependent manner. PLoS Pathog. 2010;6:e1001121. doi: 10.1371/journal.ppat.1001121. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 77.Aleksandrowicz P., Marzi A., Biedenkopf N., et al. Ebola virus enters host cells by macropinocytosis and clathrin-mediated endocytosis. J Infect Dis. 2011;204:S957–S967. doi: 10.1093/infdis/jir326. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 78.Hunt C.L., Kolokoltsov A.A., Davey R.A., et al. The tyro3 receptor kinase axl enhances macropinocytosis of zaire ebolavirus. J Virol. 2011;85:334–347. doi: 10.1128/JVI.01278-09. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 79.Eckert D.M., Kim P.S. Mechanisms of viral membrane fusion and its inhibition. Annu Rev Biochem. 2001;70:777–810. doi: 10.1146/annurev.biochem.70.1.777. [DOI] [PubMed] [Google Scholar]
  • 80.Mothes W., Boerger A.L., Narayan S., et al. Retroviral entry mediated by receptor priming and low pH triggering of an envelope glycoprotein. Cell. 2000;103(4):679–689. doi: 10.1016/S0092-8674(00)00170-7. [DOI] [PubMed] [Google Scholar]
  • 81.Bar S., Takada A., Kawaoka Y., et al. Detection of cell-cell fusion mediated by Ebola virus glycoproteins. J Virol. 2006;80(6):2815–2822. doi: 10.1128/JVI.80.6.2815-2822.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 82.Ito H., Watanabe S., Sanchez A., et al. Mutational analysis of the putative fusion domain of Ebola virus glycoprotein. J Virol. 1999;73(10):8907–8912. doi: 10.1128/jvi.73.10.8907-8912.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 83.Simmons G., Reeves J.D., Rennekamp A.J., et al. Characterization of severe acute respiratory syndrome-associated coronavirus (SARS-CoV) spike glycoprotein-mediated viral entry. Proc Natl Acad Sci USA. 2004;101(12):4240–4245. doi: 10.1073/pnas.0306446101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 84.Chandran K., Sullivan N.J., Felbor U., et al. Endosomal proteolysis of the Ebola virus glycoprotein is necessary for infection. Science. 2005;308(5728):1643–1645. doi: 10.1126/science.1110656. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 85.Schornberg K., Matsuyama S., Kabsch K., et al. Role of endosomal cathepsins in entry mediated by the Ebola virus glycoprotein. J Virol. 2006;80(8):4174–4178. doi: 10.1128/JVI.80.8.4174-4178.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 86.Misasi J., Chandran K., Yang J.Y., et al. Filoviruses require endosomal cysteine proteases for entry but exhibit distinct protease preferences. J Virol. 2012;86(6):3284–3292. doi: 10.1128/JVI.06346-11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 87.Gnirss K., Kühl A., Karsten C., et al. Cathepsins B and L activate Ebola but not Marburg virus glycoproteins for efficient entry into cell lines and macrophages independent of TMPRSS2 expression. Virology. 2012;424(1):3–10. doi: 10.1016/j.virol.2011.11.031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 88.Ebert D.H., Deussing J., Peters C., et al. Cathepsin L and cathepsin B mediate reovirus disassembly in murine fibroblast cells. J Biol Chem. 2002;277(27):24609–24617. doi: 10.1074/jbc.M201107200. [DOI] [PubMed] [Google Scholar]
  • 89.Simmons G., Gosalia D.N., Rennekamp A.J., et al. Inhibitors of cathepsin L prevent severe acute respiratory syndrome coronavirus entry. Proc Natl Acad Sci USA. 2005;102(33):11876–11881. doi: 10.1073/pnas.0505577102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 90.Qiu Z., Hingley S.T., Simmons G., et al. Endosomal proteolysis by cathepsins is necessary for murine coronavirus mouse hepatitis virus type 2 spike-mediated entry. J Virol. 2006;80(12):5768–5776. doi: 10.1128/JVI.00442-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 91.Carette J.E., Raaben M., Wong A.C., et al. Ebola virus entry requires the cholesterol transporter Niemann-Pick C1. Nature. 2011;477(7364):340–343. doi: 10.1038/nature10348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 92.Cote M., Misasi J., Ren T., et al. Small molecule inhibitors reveal Niemann-Pick C1 is essential for Ebola virus infection. Nature. 2011;477(7364):344–348. doi: 10.1038/nature10380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 93.Miller E.H., Obernosterer G., Raaben M., et al. Ebola virus entry requires the host-programmed recognition of an intracellular receptor. EMBO J. 2012;31(8):1947–1960. doi: 10.1038/emboj.2012.53. [DOI] [PMC free article] [PubMed] [Google Scholar]

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