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Junin virus (JUNV) entry is conducted by receptor-mediated endocytosis. To explore the cellular entry mechanism of JUNV, inhibitory effects of drugs affecting the main endocytic pathways on JUNV entry into Vero cells were analysed. Compounds that impair clathrin-mediated endocytosis were shown to reduce virus internalization without affecting virion binding. In contrast, drugs that alter lipid-raft microdomains, impairing caveola-mediated endocytosis, were not able to block virus entry. To show direct evidence of JUNV entry, transmission electron microscopy was performed; it showed JUNV particles of about 60-100 nm in membrane depressions that had an electron-dense coating, In addition, JUNV particles were found within invaginations of the plasma membrane and vesicles that resembled those of pits and clathrin-coated vesicles. Taken together, these results demonstrate that clathrin-mediated endocytosis is the main JUNV entry pathway into Vero cells and represent an important contribution to the characterization of the arenavirus multiplication cycle. © 2007 SGM.


Documento: Artículo
Título:Characterization of Junin arenavirus cell entry
Autor:Martinez, M.G.; Cordo, S.M.; Candurra, N.A.
Filiación:Laboratorio de Virología, Departamento de Química Biológica, Universidad de Buenos Aires (UBA), Pabellón II, Piso 4, 1428 Buenos Aires, Argentina
Palabras clave:clathrin; animal cell; article; caveola; cell transport; controlled study; endocytosis; Junin virus; lipid raft; membrane vesicle; nonhuman; pathogenesis; priority journal; transmission electron microscopy; transport kinetics; Vero cell; virogenesis; virus cell interaction; virus infection; virus inhibition; virus particle; Animals; Caveolae; Cell Membrane; Cercopithecus aethiops; Chlorpromazine; Clathrin-Coated Vesicles; Endocytosis; Junin virus; Microscopy, Electron, Transmission; Vero Cells; Virion; Virus Attachment; Virus Internalization; Arenavirus; Junin virus
Página de inicio:1776
Página de fin:1784
Título revista:Journal of General Virology
Título revista abreviado:J. Gen. Virol.
CAS:Chlorpromazine, 50-53-3


  • Bishop, N.E., An update on non-clathrin-coated endocytosis (1997) Rev Med Virol, 7, pp. 199-209
  • Borrow, P., Oldstone, M.B., Characterization of lymphocytic choriomeningitis virus-binding protein(s): A candidate cellular receptor for the virus (1992) J Virol, 66, pp. 7270-7281
  • Borrow, P., Oldstone, M.B., Mechanism of lymphocytic choriomeningitis virus entry into cefls (1994) Virology, 198, pp. 1-9
  • Bowen, M.D., Peters, C.J., Nichol, S.T., The phylogeny of New World (Tacaribe complex) arenaviruses (1996) Virology, 219, pp. 285-290
  • Bowen, M.D., Peters, C.J., Nichol, S.T., Phylogenetic analysis of the Arenaviridae: Patterns of virus evolution and evidence for cospeciation between arenaviruses and their rodent hosts (1997) Mol Phylogenet Evol, 8, pp. 301-316
  • Brodsky, F.M., Chen, C.Y., Knuehl, C., Towler, M.C., Wakeham, D.E., Biological basket weaving: Formation and function of clathrin-coated vesicles (2001) Annu Rev Cell Dev Biol, 17, pp. 517-568
  • Candurra, N.A., Damonte, E.B., Effect of inhibitors of the intracellular exocytic pathway on glycoprotein processing and maturation of Junin virus (1997) Arch Virol, 142, pp. 2179-2193
  • Castilla, V., Mersich, S.E., Candurra, N.A., Damonte, E.B., The entry of Junin virus into Vero cells (1994) Arch Virol, 136, pp. 363-374
  • Charrel, R.N., de Lamballerie, X., Arenaviruses other than Lassa virus (2003) Antiviral Res, 57, pp. 89-100
  • Charrel, R.N., Feldmann, H., Fulhorst, C.F., Khelifa, R., de Chesse, R., de Lamballerie, X., Phylogeny of New World arenaviruses based on the complete coding sequences of the small genomic segment identified an evolutionary lineage produced by intrasegmental recombination (2002) Biochem Biophys Res Commun, 296, pp. 1118-1124
  • Conner, S.D., Schmid, S.L., Regulated portals of entry into the cell (2003) Nature, 422, pp. 37-44
  • Crowther, R.A., Finch, J.T., Pearse, B.M., On the structure of coated vesicles (1976) J Mol Biol, 103, pp. 785-798
  • Damonte, E.B., Mersich, S.E., Candurra, N.A., Coto, C.E., Cross reactivity between Junin and Tacaribe viruses as determined by neutralization test and immunoprecipitation (1986) Med Microbiol Immunol, 175, pp. 85-88
  • Damonte, E.B., Mersich, S.E., Candurra, N.A., Intracellular processing and transport of Junin virus glycoproteins influences virion infectivity (1994) Virus Res, 34, pp. 317-326
  • DeTulleo, L., Kirchhausen, T., The clathrin endocytic pathway in viral infection (1998) EMBO J, 17, pp. 4585-4593
  • Ehrlich, M., Boll, W., Van Oijen, A., Hariharan, R., Chandran, K., Nibert, M.L., Kirchhausen, T., Endocytosis by random initiation and stabilization of clathrin-coated pits (2004) Cell, 118, pp. 591-605
  • Helenius, A., Kartenbeck, J., Simons, K., Fries, E., On the entry of Semliki Forest virus into BHK-21 cells (1980) J Cell Biol, 84, pp. 404-420
  • Heuser, J.E., Anderson, R.G., Hypertonic media inhibit receptor-mediated endocytosis by blocking clathrin-coated pit formation (1989) J Cell Biol, 108, pp. 389-400
  • Jin, M., Park, J., Lee, S., Park, B., Shin, J., Song, K.J., Ahn, T.I., Ahn, K., Hantaan virus enters cells by clathrin-dependent receptor-mediated endocytosis (2002) Virology, 294, pp. 60-69
  • Kee, S.H., Cho, E.J., Song, J.W., Park, K.S., Baek, L.J., Song, K.J., Effects of endocytosis inhibitory drugs on rubella virus entry into VeroE6 cells (2004) Microbiol Immunol, 48, pp. 823-829
  • Liebl, D., Difato, F., Hornikova, L., Mannova, P., Stokrova, J., Forstova, J., Mouse polyomavirus enters early endosomes, requires their acidic pH for productive infection, and meets transferrin cargo in Rab 11 -positive endosomes (2006) J Virol, 80, pp. 4610-4622
  • Madshus, I.H., Sandvig, K., Olsnes, S., van Deurs, B., Effect of reduced endocytosis induced by hypotonic shock and potassium depletion on the infection of Hep 2 cells by picornaviruses (1987) J Cell Physiol, 131, pp. 14-22
  • Maiztegui, J. I., McKee, K. T., Jr, Barrera Oro, J. G., Harrison, L. H., Gibbs, P. H., Feuillade, M. R., Enria, D. A., Briggiler, A. M., Levis, S. C. & other authors (1998). Protective efficacy of a live attenuated vaccine against Argentine hemorrhagic fever. AHF Study Group. J Infect Dis 177, 277-283; Marechal, V., Prevost, M.C., Petit, C., Perret, E., Heard, J.M., Schwartz, O., Human immunodeficiency virus type 1 entry into macrophages mediated by macropinocytosis (2001) J Virol, 75, pp. 11166-11177
  • Marsh, M., Helenius, A., Adsorptive endocytosis of Semliki Forest virus (1980) J Mol Biol, 142, pp. 439-454
  • Matlin, K.S., Reggio, H., Helenius, A., Simons, K., Infectious entry pathway of influenza virus in a canine kidney cell line (1981) J Cell Biol, 91, pp. 601-613
  • Matlin, K.S., Reggio, H., Helenius, A., Simons, K., Pathway of vesicular stomatitis virus entry leading to infection (1982) J Mol Biol, 156, pp. 609-631
  • Miller, N., Hutt-Fletcher, L.M., Epstein-Barr virus enters B cells and epithelial cells by different routes (1992) J Virol, 66, pp. 3409-3414
  • Murphy, F.A., Webb, P.A., Johnson, K.M., Whitfield, S.G., Chappell, W.A., Arenoviruses in Vero cells: Ultrastructural studies (1970) J Virol, 6, pp. 507-518
  • Nichols, B., Caveosomes and endocytosis of lipid rafts (2003) J Cell Sci, 116, pp. 4707-4714
  • Nichols, B.J., Lippincott-Schwartz, J., Endocytosis without clathrin coats (2001) Trends Cell Biol, 11, pp. 406-412
  • Parodi, A.S., Greenway, D.J., Rugiero, H.R., Frigeria, M., De La Barrera, J.M., Mettler, N., Garzon, F., Nota, N., Concerning the epidemic outbreak in Junin (1958) Dia Med, 30, pp. 2300-2301. , in Spanish
  • Pelkmans, L., Helenius, A., Insider information: What viruses tell us about endocytosis (2003) Curr Opin Cell Biol, 15, pp. 414-422
  • Pelkmans, L., Kartenbeck, J., Helenius, A., Caveolar endocytosis of simian virus 40 reveals a new two-step vesicular-transport pathway to the ER (2001) Nat Cell Biol, 3, pp. 473-483
  • Peters, C.J., Human infection with arenaviruses in the Americas (2002) Curr Top Microbiol Immunol, 262, pp. 65-74
  • Radoshitzky, S. R., Abraham, J., Spiropoulou, C. F., Kuhn, J. H., Nguyen, D., Li, W., Nagel, J., Schmidt, P. J., Nunberg, J. H. & other authors (2007). Transferrin receptor I is a cellular receptor for New World haemorrhagic fever arenaviruses. Nature 446, 92-96; Reignier, T., Oldenburg, J., Noble, B., Lamb, E., Romanowski, V., Buchmeier, M.J., Cannon, P.M., Receptor use by pathogenic arenaviruses (2006) Virology, 353, pp. 111-120
  • Rodal, S.K., Skretting, G., Garred, O., Vilhardt, F., van Deurs, B., Sandvig, K., Extraction of cholesterol with methyl-beta-cyclodextrin perturbs formation of clathrin-coated endocytic vesicles (1999) Mol Biol Cell, 10, pp. 961-974
  • Rojek, J.M., Spiropoulou, C.F., Kunz, S., Characterization of the cellular receptors for the South American hemorrhagic fever viruses Junin, Guanarito, and Machupo (2006) Virology, 349, pp. 476-491
  • Rust, M.J., Lakadamyali, M., Zhang, F., Zhuang, X., Assembly of endocytic machinery around individual influenza viruses during viral entry (2004) Nat Struct Mol Biol, 11, pp. 567-573
  • Sanchez, A., Pifat, D.Y., Kenyon, R.H., Peters, C.J., McCormick, J.B., Kiley, M.P., Junin virus monoclonal antibodies: Characterization and cross-reactivity with other arenaviruses (1989) J Gen Virol, 70, pp. 1125-1132
  • Shah, W.A., Peng, H., Carbonetto, S., Role of non-raft cholesterol in lymphocytic choriomeningitis virus infection via alpha-dystroglycan (2006) J Gen Virol, 87, pp. 673-678
  • Sieczkarski, S.B., Whittaker, G.R., Dissecting virus entry via endocytosis (2002) J Gen Virol, 83, pp. 1535-1545
  • Sieczkarski, S.B., Whittaker, G.R., Influenza virus can enter and infect cells in the absence of clathrin-mediated endocytosis (2002) J Virol, 76, pp. 10455-10464
  • Spiropoulou, C.F., Kunz, S., Rollin, P.E., Campbell, K.P., Oldstone, M.B., New World arenavirus clade C, but not clade A and B viruses, utilizes alpha- dystroglycan as its major receptor (2002) J Virol, 76, pp. 5140-5146
  • Stuart, A.D., Eustace, H.E., McKee, T.A., Brown, T.D., A novel cell entry pathway for a DAF-using human enterovirus is dependent on lipid rafts (2002) J Virol, 76, pp. 9307-9322
  • Subtil, A., Gaidarov, L., Kobylarz, K., Lampson, M.A., Keen, J.H., McGraw, T.E., Acute cholesterol depletion inhibits clathrin-coated pit budding (1999) Proc Natl Acad Sci U S A, 96, pp. 6775-6780
  • Torgersen, M.L., Skretting, G., van Deurs, B., Sandvig, K., Internalization of cholera toxin by different endocytic mechanisms (2001) J Cell Sci, 114, pp. 3737-3747
  • Wang, L.H., Rothberg, K.G., Anderson, R.G., Mis-assembly of clathrin lattices on endosomes reveals a regulatory switch for coated pit formation (1993) J Cell Biol, 123, pp. 1107-1117
  • Weissenbacher, M.C., Laguens, R.P., Coto, C.E., Argentine hemorrhagic fever (1987) Curr Top Microbiol Immunol, 134, pp. 79-116
  • York, J., Romanowski, V., Lu, M., Nunberg, J.H., The signal peptide of the Junin arenavirus envelope glycoprotein is myristoylated and forms an essential subunit of the mature G1-G2 complex (2004) J Virol, 78, pp. 10783-10792


---------- APA ----------
Martinez, M.G., Cordo, S.M. & Candurra, N.A. (2007) . Characterization of Junin arenavirus cell entry. Journal of General Virology, 88(6), 1776-1784.
---------- CHICAGO ----------
Martinez, M.G., Cordo, S.M., Candurra, N.A. "Characterization of Junin arenavirus cell entry" . Journal of General Virology 88, no. 6 (2007) : 1776-1784.
---------- MLA ----------
Martinez, M.G., Cordo, S.M., Candurra, N.A. "Characterization of Junin arenavirus cell entry" . Journal of General Virology, vol. 88, no. 6, 2007, pp. 1776-1784.
---------- VANCOUVER ----------
Martinez, M.G., Cordo, S.M., Candurra, N.A. Characterization of Junin arenavirus cell entry. J. Gen. Virol. 2007;88(6):1776-1784.