Skip to main content
PMC home page
Virologica Sinica logoLink to Virologica Sinica
. 2016 Aug 4;31(5):380–394. doi: 10.1007/s12250-016-3815-4

Structure-function relationship of the mammarenavirus envelope glycoprotein

Wei Wang 1,✉, Zheng Zhou 1, Leike Zhang 1, Shaobo Wang 1, Gengfu Xiao 1
PMCID: PMC8193374  PMID: 27562602

Abstract

Mammarenaviruses, including lethal pathogens such as Lassa virus and Junín virus, can cause severe hemorrhagic fever in humans. Entry is a key step for virus infection, which starts with binding of the envelope glycoprotein (GP) to receptors on target cells and subsequent fusion of the virus with target cell membranes. The GP precursor is synthesized as a polypeptide, and maturation occurs by two cleavage events, yielding a tripartite GP complex (GPC) formed by a stable signal peptide (SSP), GP1 and GP2. The unique retained SSP interacts with GP2 and plays essential roles in virion maturation and infectivity. GP1 is responsible for binding to the cell receptor, and GP2 is a class I fusion protein. The native structure of the tripartite GPC is unknown. GPC is critical for the receptor binding, membrane fusion and neutralization antibody recognition. Elucidating the molecular mechanisms underlining the structure–function relationship of the three subunits is the key for understanding their function and can facilitate novel avenues for combating virus infections. This review summarizes the basic aspects and recent research of the structure–function relationship of the three subunits. We discuss the structural basis of the receptor-binding domain in GP1, the interaction between SSP and GP2 and its role in virion maturation and membrane fusion, as well as the mechanism by which glycosylation stabilizes the GPC structure and facilitates immune evasion. Understanding the molecular mechanisms involved in these aspects will contribute to the development of novel vaccines and treatment strategies against mammarenaviruses infection.

graphic file with name 12250_2016_3815_Fig1_HTML.jpg

Keywords: Mammarenaviruses, glycoprotein complex (GPC), stable signal peptide (SSP), membrane fusion, glycosylation

Footnotes

ORCID: 0000-0002-8696-9773

References

  1. Abraham J, Corbett KD, Farzan M, Choe H, Harrison SC. Structural basis for receptor recognition by New World hemorrhagic fever arenaviruses. Nat Struct Mol Biol. 2010;17:438–444. doi: 10.1038/nsmb.1772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Abraham J, Kwong JA, Albarino CG, Lu JG, Radoshitzky SR, Salazar-Bravo J, Farzan M, Spiropoulou CF, Choe H. Hostspecies transferrin receptor 1 orthologs are cellular receptors for nonpathogenic new world clade B arenaviruses. PLoS Pathog. 2009;5:e1000358. doi: 10.1371/journal.ppat.1000358. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Agnihothram SS, York J, Nunberg JH. Role of the stable signal peptide and cytoplasmic domain of G2 in regulating intracellular transport of the Junin virus envelope glycoprotein complex. J Virol. 2006;80:5189–5198. doi: 10.1128/JVI.00208-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Agnihothram SS, York J, Trahey M, Nunberg JH. Bitopic membrane topology of the stable signal peptide in the tripartite Junin virus GP-C envelope glycoprotein complex. J Virol. 2007;81:4331–4337. doi: 10.1128/JVI.02779-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Albarino CG, Bird BH, Chakrabarti AK, Dodd KA, Flint M, Bergeron E, White DM, Nichol ST. The major determinant of attenuation in mice of the Candid1 vaccine for Argentine hemorrhagic fever is located in the G2 glycoprotein transmembrane domain. J Virol. 2011;85:10404–10408. doi: 10.1128/JVI.00856-11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Albarino CG, Bird BH, Chakrabarti AK, Dodd KA, White DM, Bergeron E, Shrivastava-Ranjan P, Nichol ST. Reverse genetics generation of chimeric infectious Junin/Lassa virus is dependent on interaction of homologous glycoprotein stable signal peptide and G2 cytoplasmic domains. J Virol. 2011;85:112–122. doi: 10.1128/JVI.01837-10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Armstrong C, Lillie RD. Experimental lymphocytic choriomeningitis of monkeys and mice produced by a virus encountered in studies of the 1933 St Louis encephalitis epidemic. Public Health Rep. 1934;49:1019–1027. doi: 10.2307/4581290. [DOI] [Google Scholar]
  8. Bederka LH, Bonhomme CJ, Ling EL, Buchmeier MJ. Arenavirus stable signal peptide is the keystone subunit for glycoprotein complex organization. MBio. 2014;5:e02063. doi: 10.1128/mBio.02063-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bedossa P, Ferlicot S, Paradis V, Dargere D, Bonvoust F, Vidaud M. Dystroglycan expression in hepatic stellate cells: role in liver fibrosis. Lab Invest. 2002;82:1053–1061. doi: 10.1097/01.LAB.0000024429.73158.DE. [DOI] [PubMed] [Google Scholar]
  10. Beyer WR, Popplau D, Garten W v, Laer D, Lenz O. Endoproteolytic processing of the lymphocytic choriomeningitis virus glycoprotein by the subtilase SKI-1/S1P. J Virol. 2003;77:2866–2872. doi: 10.1128/JVI.77.5.2866-2872.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Bolken TC, Laquerre S, Zhang Y, Bailey TR, Pevear DC, Kickner SS, Sperzel LE, Jones KF, Warren T A, Lund S, Kirkwood-Watts DL, King DS, Shurtleff AC, Guttieri MC, Deng Y, Bleam M, Hruby DE. Identification and characterization of potent small molecule inhibitor of hemorrhagic fever New World arenaviruses. Antiviral Res. 2006;69:86–97. doi: 10.1016/j.antiviral.2005.10.008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Bonhomme CJ, Capul AA, Lauron EJ, Bederka LH, Knopp KA, Buchmeier MJ. Glycosylation modulates arenavirus glycoprotein expression and function. Virology. 2011;409:223–233. doi: 10.1016/j.virol.2010.10.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Bonhomme CJ, Knopp KA, Bederka LH, Angelini MM, Buchmeier MJ. LCMV glycosylation modulates viral fitness and cell tropism. PLoS One. 2013;8:e53273. doi: 10.1371/journal.pone.0053273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Borrow P, Oldstone MB. Mechanism of lymphocytic choriomeningitis virus entry into cells. Virology. 1994;198:1–9. doi: 10.1006/viro.1994.1001. [DOI] [PubMed] [Google Scholar]
  15. Bowden TA, Crispin M, Graham SC, Harvey DJ, Grimes JM, Jones EY, Stuart DI. Unusual molecular architecture of the machupo virus attachment glycoprotein. J Virol. 2009;83:8259–8265. doi: 10.1128/JVI.00761-09. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Bowen MD, Peters CJ, Nichol ST. The phylogeny of New World (Tacaribe complex) arenaviruses. Virology. 1996;219:285–290. doi: 10.1006/viro.1996.0248. [DOI] [PubMed] [Google Scholar]
  17. Bowen MD, Peters CJ, Nichol ST. Phylogenetic analysis of the Arenaviridae: patterns of virus evolution and evidence for cospeciation between arenaviruses and their rodent hosts. Mol Phylogenet Evol. 1997;8:301–316. doi: 10.1006/mpev.1997.0436. [DOI] [PubMed] [Google Scholar]
  18. Braakman I, van Anken E. Folding of viral envelope glycoproteins in the endoplasmic reticulum. Traffic. 2000;1:533–539. doi: 10.1034/j.1600-0854.2000.010702.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Branco LM, Grove JN, Moses LM, Goba A, Fullah M, Momoh M, Schoepp RJ, Bausch DG, Garry RF. Shedding of soluble glycoprotein 1 detected during acute Lassa virus infection in human subjects. Virol J. 2010;7:306. doi: 10.1186/1743-422X-7-306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Briknarova K, Thomas CJ, York J, Nunberg JH. Structure of a zinc-binding domain in the Junin virus envelope glycoprotein. J Biol Chem. 2011;286:1528–1536. doi: 10.1074/jbc.M110.166025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Buchmeier MJ, de la Torre JC, Peters CJ. Fields Virology. 2007. pp. 1791–1828. [Google Scholar]
  22. Burns JW, Buchmeier MJ. Protein-protein interactions in lymphocytic choriomeningitis virus. Virology. 1991;183:620–629. doi: 10.1016/0042-6822(91)90991-J. [DOI] [PubMed] [Google Scholar]
  23. Burri D d, Palma JR, Seidah NG, Zanotti G, Cendron L, Pasquato A, Kunz S. Differential recognition of Old World and New World arenavirus envelope glycoproteins by subtilisin kexin isozyme 1 (SKI-1)/site 1 protease (S1P) J Virol. 2013;87:6406–6414. doi: 10.1128/JVI.00072-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Burri DJ, Pasqual G, Rochat C, Seidah NG, Pasquato A, Kunz S. Molecular characterization of the processing of arenavirus envelope glycoprotein precursors by subtilisin kexin isozyme-1/site-1 protease. J Virol. 2012;86:4935–4946. doi: 10.1128/JVI.00024-12. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Cajimat MN, Milazzo ML, Rollin PE, Nichol ST, Bowen MD, Ksiazek TG, Fulhorst CF. Genetic diversity among Bolivian arenaviruses. Virus Res. 2009;140:24–31. doi: 10.1016/j.virusres.2008.10.016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Cao W, Henry MD, Borrow P, Yamada H, Elder JH, Ravkov EV, Nichol ST, Compans RW, Campbell KP, Oldstone MB. Identification of alpha-dystroglycan as a receptor for lymphocytic choriomeningitis virus and Lassa fever virus. Science. 1998;282:2079–2081. doi: 10.1126/science.282.5396.2079. [DOI] [PubMed] [Google Scholar]
  27. Cashman KA, Smith MA, Twenhafel NA, Larson RA, Jones KF, Allen R 3, Dai D, Chinsangaram J, Bolken TC, Hruby DE, Amberg SM, Hensley LE, Guttieri MC. Evaluation of Lassa antiviral compound ST-193 in a guinea pig model. Antiviral Res. 2011;90:70–79. doi: 10.1016/j.antiviral.2011.02.012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Charrel RN, Feldmann H, Fulhorst CF, 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. Biochem Biophys Res Commun. 2002;296:1118–1124. doi: 10.1016/S0006-291X(02)02053-3. [DOI] [PubMed] [Google Scholar]
  29. Clegg JC. Molecular phylogeny of the arenaviruses. Curr Top Microbiol Immunol. 2002;262:1–24. doi: 10.1007/978-3-642-56029-3_1. [DOI] [PubMed] [Google Scholar]
  30. Cohen-Dvashi H, Cohen N, Israeli H, Diskin R. Molecular Mechanism for LAMP1 Recognition by Lassa Virus. J Virol. 2015;89:7584–7592. doi: 10.1128/JVI.00651-15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Cosset FL, Marianneau P, Verney G, Gallais F, Tordo N, Pecheur E t, Meulen J, Deubel V, Bartosch B. Characterization of Lassa virus cell entry and neutralization with Lassa virus pseudoparticles. J Virol. 2009;83:3228–3237. doi: 10.1128/JVI.01711-08. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. da Palma JR, Burri DJ, Oppliger J, Salamina M, Cendron L, de Laureto PP, Seidah NG, Kunz S, Pasquato A. Zymogen activation and subcellular activity of subtilisin kexin isozyme 1/site 1 protease. J Biol Chem. 2014;289:35743–35756. doi: 10.1074/jbc.M114.588525. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Di Simone C, Zandonatti MA, Buchmeier MJ. Acidic pH triggers LCMV membrane fusion activity and conformational change in the glycoprotein spike. Virology. 1994;198:455–465. doi: 10.1006/viro.1994.1057. [DOI] [PubMed] [Google Scholar]
  34. Droniou-Bonzom ME, Reignier T, Oldenburg JE, Cox AU, Exline CM, Rathbun JY, Cannon PM. Substitutions in the glycoprotein (GP) of the Candid#1 vaccine strain of Junin virus increase dependence on human transferrin receptor 1 for entry and destabilize the metastable conformation of GP. J Virol. 2011;85:13457–13462. doi: 10.1128/JVI.05616-11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Eichler R, Lenz O, Garten W, Strecker T. The role of single N-glycans in proteolytic processing and cell surface transport of the Lassa virus glycoprotein GP-C. Virol J. 2006;3:41. doi: 10.1186/1743-422X-3-41. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Eichler R, Lenz O, Strecker T, Eickmann M, Klenk HD, Garten W. Identification of Lassa virus glycoprotein signal peptide as a trans-acting maturation factor. EMBO Rep. 2003;4:1084–1088. doi: 10.1038/sj.embor.7400002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Eichler R, Lenz O, Strecker T, Eickmann M, Klenk HD, Garten W. Lassa virus glycoprotein signal peptide displays a novel topology with an extended endoplasmic reticulum luminal region. J Biol Chem. 2004;279:12293–12299. doi: 10.1074/jbc.M312975200. [DOI] [PubMed] [Google Scholar]
  38. Eichler R, Lenz O, Strecker T, Garten W. Signal peptide of Lassa virus glycoprotein GP-C exhibits an unusual length. FEBS Lett. 2003;538:203–206. doi: 10.1016/S0014-5793(03)00160-1. [DOI] [PubMed] [Google Scholar]
  39. Eichler R, Strecker T, Kolesnikova L t, Meulen J, Weissenhorn W, Becker S, Klenk HD, Garten W, Lenz O. Characterization of the Lassa virus matrix protein Z: electron microscopic study of virus-like particles and interaction with the nucleoprotein (NP) Virus Res. 2004;100:249–255. doi: 10.1016/j.virusres.2003.11.017. [DOI] [PubMed] [Google Scholar]
  40. Emonet S, Lemasson JJ, Gonzalez JP, de Lamballerie X, Charrel RN. Phylogeny and evolution of old world arenaviruses. Virology. 2006;350:251–257. doi: 10.1016/j.virol.2006.01.026. [DOI] [PubMed] [Google Scholar]
  41. Enria D B, Oro JG. Junin virus vaccines. Curr Top Microbiol Immunol. 2002;263:239–261. doi: 10.1007/978-3-642-56055-2_12. [DOI] [PubMed] [Google Scholar]
  42. Eschli B, Quirin K, Wepf A, Weber J, Zinkernagel R, Hengartner H. Identification of an N-terminal trimeric coiled-coil core within arenavirus glycoprotein 2 permits assignment to class I viral fusion proteins. J Virol. 2006;80:5897–5907. doi: 10.1128/JVI.00008-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Eschli B, Zellweger RM, Wepf A, Lang KS, Quirin K, Weber J, Zinkernagel RM, Hengartner H. Early antibodies specific for the neutralizing epitope on the receptor binding subunit of the lymphocytic choriomeningitis virus glycoprotein fail to neutralize the virus. J Virol. 2007;81:11650–11657. doi: 10.1128/JVI.00955-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Fisher-Hoch SP, McCormick JB. Towards a human Lassa fever vaccine. Rev Med Virol. 2001;11:331–341. doi: 10.1002/rmv.329. [DOI] [PubMed] [Google Scholar]
  45. Flanagan ML, Oldenburg J, Reignier T, Holt N, Hamilton GA, Martin VK, Cannon PM. New world clade B arenaviruses can use transferrin receptor 1 (TfR1)-dependent and -independent entry pathways, and glycoproteins from human pathogenic strains are associated with the use of TfR1. J Virol. 2008;82:938–948. doi: 10.1128/JVI.01397-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Froeschke M, Basler M, Groettrup M, Dobberstein B. Long-lived signal peptide of lymphocytic choriomeningitis virus glycoprotein pGP-C. J Biol Chem. 2003;278:41914–41920. doi: 10.1074/jbc.M302343200. [DOI] [PubMed] [Google Scholar]
  47. Fuller-Pace FV, Southern PJ. Detection of virus-specific RNA-dependent RNA polymerase activity in extracts from cells infected with lymphocytic choriomeningitis virus: in vitro synthesis of full-length viral RNA species. J Virol. 1989;63:1938–1944. doi: 10.1128/jvi.63.5.1938-1944.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Garces F, Lee JH, de Val N T, de la Pena A, Kong L, Puchades C, Hua Y, Stanfield RL, Burton DR, Moore JP, Sanders RW, Ward AB, Wilson IA. Affinity Maturation of a Potent Family of HIV Antibodies Is Primarily Focused on Accommodating or Avoiding Glycans. Immunity. 2015;43:1053–1063. doi: 10.1016/j.immuni.2015.11.007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Garces F, Sok D, Kong L, McBride R, Kim HJ, Saye-Francisco KF, Julien JP, Hua Y, Cupo A, Moore JP, Paulson JC, Ward AB, Burton DR, Wilson IA. Structural evolution of glycan recognition by a family of potent HIV antibodies. Cell. 2014;159:69–79. doi: 10.1016/j.cell.2014.09.009. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Garcin D, Kolakofsky D. A novel mechanism for the initiation of Tacaribe arenavirus genome replication. J Virol. 1990;64:6196–6203. doi: 10.1128/jvi.64.12.6196-6203.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Goncalves AR, Moraz ML, Pasquato A, Helenius A, Lozach PY, Kunz S. Role of DC-SIGN in Lassa virus entry into human dendritic cells. J Virol. 2013;87:11504–11515. doi: 10.1128/JVI.01893-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Gunther S, Emmerich P, Laue T, Kuhle O, Asper M, Jung A, Grewing T t, Meulen J, Schmitz H. Imported lassa fever in Germany: molecular characterization of a new lassa virus strain. Emerg Infect Dis. 2000;6:466–476. doi: 10.3201/eid0605.000504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Hara Y, Kanagawa M, Kunz S, Yoshida-Moriguchi T, Satz JS, Kobayashi YM, Zhu Z, Burden SJ, Oldstone MB, Campbell KP. Like-acetylglucosaminyltransferase (LARGE)-dependent modification of dystroglycan at Thr-317/319 is required for laminin binding and arenavirus infection. Proc Natl Acad Sci U S A. 2011;108:17426–17431. doi: 10.1073/pnas.1114836108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Harrison SC. Viral membrane fusion. Nat Struct Mol Biol. 2008;15:690–698. doi: 10.1038/nsmb.1456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Hastie KM, Igonet S, Sullivan BM, Legrand P, Zandonatti MA, Robinson JE, Garry RF, Rey FA, Oldstone MB, Saphire EO. Crystal structure of the prefusion surface glycoprotein of the prototypic arenavirus LCMV. Nat Struct Mol Biol. 2016;23:513–521. doi: 10.1038/nsmb.3210. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Igonet S, Vaney MC, Vonrhein C, Bricogne G, Stura EA, Hengartner H, Eschli B, Rey FA. X-ray structure of the arenavirus glycoprotein GP2 in its postfusion hairpin conformation. Proc Natl Acad Sci U S A. 2011;108:19967–19972. doi: 10.1073/pnas.1108910108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Imperiali M, Thoma C, Pavoni E, Brancaccio A, Callewaert N, Oxenius A. O Mannosylation of alpha-dystroglycan is essential for lymphocytic choriomeningitis virus receptor function. J Virol. 2005;79:14297–14308. doi: 10.1128/JVI.79.22.14297-14308.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Jae LT, Raaben M, Herbert AS, Kuehne AI, Wirchnianski AS, Soh TK, Stubbs SH, Janssen H, Damme M, Saftig P, Whelan SP, Dye JM, Brummelkamp TR. Lassa virus entry requires a trigger-induced receptor switch. Science. 2014;344:1506–1510. doi: 10.1126/science.1252480. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Jae LT, Raaben M, Riemersma M, van Beusekom E, Blomen VA, Velds A, Kerkhoven RM, Carette JE, Topaloglu H, Meinecke P, Wessels MW, Lefeber DJ, Whelan SP, van Bokhoven H, Brummelkamp TR. Deciphering the glycosylome of dystroglycanopathies using haploid screens for lassa virus entry. Science. 2013;340:479–483. doi: 10.1126/science.1233675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Johnson KM, McCormick JB, Webb PA, Smith ES, Elliott LH, King IJ. Clinical virology of Lassa fever in hospitalized patients. J Infect Dis. 1987;155:456–464. doi: 10.1093/infdis/155.3.456. [DOI] [PubMed] [Google Scholar]
  61. Klewitz C, Klenk H t, Meulen J. Amino acids from both N-terminal hydrophobic regions of the Lassa virus envelope glycoprotein GP-2 are critical for pH-dependent membrane fusion and infectivity. J Gen Virol. 2007;88:2320–2328. doi: 10.1099/vir.0.82950-0. [DOI] [PubMed] [Google Scholar]
  62. Kong L, Lee JH, Doores KJ, Murin CD, Julien JP, McBride R, Liu Y, Marozsan A, Cupo A, Klasse PJ, Hoffenberg S, Caulfield M, King CR, Hua Y, Le KM, Khayat R, Deller MC, Clayton T, Tien H, Feizi T, Sanders RW, Paulson JC, Moore JP, Stanfield RL, Burton DR, Ward AB, Wilson IA. Supersite of immune vulnerability on the glycosylated face of HIV-1 envelope glycoprotein gp120. Nat Struct Mol Biol. 2013;20:796–803. doi: 10.1038/nsmb.2594. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Kranzusch PJ, Whelan SP. Architecture and regulation of negative-strand viral enzymatic machinery. RNA Biol. 2012;9:941–948. doi: 10.4161/rna.20345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Kunz S, Edelmann KH, de la Torre JC, Gorney R, Oldstone MB. Mechanisms for lymphocytic choriomeningitis virus glycoprotein cleavage, transport, and incorporation into virions. Virology. 2003;314:168–178. doi: 10.1016/S0042-6822(03)00421-5. [DOI] [PubMed] [Google Scholar]
  65. Kunz S, Rojek JM, Kanagawa M, Spiropoulou CF, Barresi R, Campbell KP, Oldstone MB. Posttranslational modification of alpha-dystroglycan, the cellular receptor for arenaviruses, by the glycosyltransferase LARGE is critical for virus binding. J Virol. 2005;79:14282–14296. doi: 10.1128/JVI.79.22.14282-14296.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Landau M, Mayrose I, Rosenberg Y, Glaser F, Martz E, Pupko T, Ben-Tal N. ConSurf 2005: the projection of evolutionary conservation scores of residues on protein structures. Nucleic Acids Res. 2005;33:W299–W302. doi: 10.1093/nar/gki370. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Larson RA, Dai D, Hosack VT, Tan Y, Bolken TC, Hruby DE, Amberg SM. Identification of a broad-spectrum arenavirus entry inhibitor. J Virol. 2008;82:10768–10775. doi: 10.1128/JVI.00941-08. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Lee AM, Rojek JM, Spiropoulou CF, Gundersen AT, Jin W, Shaginian A, York J, Nunberg JH, Boger DL, Oldstone MB, Kunz S. Unique small molecule entry inhibitors of hemorrhagic fever arenaviruses. J Biol Chem. 2008;283:18734–18742. doi: 10.1074/jbc.M802089200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Lenz O t, Meulen J, Klenk HD, Seidah NG, Garten W. The Lassa virus glycoprotein precursor GP-C is proteolytically processed by subtilase SKI-1/S1P. Proc Natl Acad Sci U S A. 2001;98:12701–12705. doi: 10.1073/pnas.221447598. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Leung WC, Leung MF, Rawls WE. Distinctive RNA transcriptase, polyadenylic acid polymerase, and polyuridylic acid polymerase activities associated with Pichinde virus. J Virol. 1979;30:98–107. doi: 10.1128/jvi.30.1.98-107.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Li S, Sun Z, Pryce R, Parsy ML, Fehling SK, Schlie K, Siebert CA, Garten W, Bowden TA, Strecker T, Huiskonen JT. Acidic pH-Induced Conformations and LAMP1 Binding of the Lassa Virus Glycoprotein Spike. PLoS Pathog. 2016;12:e1005418. doi: 10.1371/journal.ppat.1005418. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Maiztegui JI, McKee K Jr, Barrera Oro JG, Harrison LH, Gibbs PH, Feuillade MR, Enria DA, Briggiler AM, Levis SC, Ambrosio AM, Halsey NA, Peters CJ. Protective efficacy of a live attenuated vaccine against Argentine hemorrhagic fever. AHF Study Group. J Infect Dis. 1998;177:277–283. doi: 10.1086/514211. [DOI] [PubMed] [Google Scholar]
  73. Martinez MG, Bialecki MA, Belouzard S, Cordo SM, Candurra NA, Whittaker GR. Utilization of human DC-SIGN and LSIGN for entry and infection of host cells by the New World arenavirus, Junin virus. Biochem Biophys Res Commun. 2013;441:612–617. doi: 10.1016/j.bbrc.2013.10.106. [DOI] [PMC free article] [PubMed] [Google Scholar]
  74. Martinez MG, Cordo SM, Candurra NA. Characterization of Junin arenavirus cell entry. J Gen Virol. 2007;88:1776–1784. doi: 10.1099/vir.0.82808-0. [DOI] [PubMed] [Google Scholar]
  75. McCormick JB, King IJ, Webb PA, Scribner CL, Craven RB, Johnson KM, Elliott LH, Belmont-Williams R. Lassa fever. Effective therapy with ribavirin. N Engl J Med. 1986;314:20–26. doi: 10.1056/NEJM198601023140104. [DOI] [PubMed] [Google Scholar]
  76. Messina EL, York J, Nunberg JH. Dissection of the role of the stable signal peptide of the arenavirus envelope glycoprotein in membrane fusion. J Virol. 2012;86:6138–6145. doi: 10.1128/JVI.07241-11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Meulen J, Badusche M, Satoguina J, Strecker T, Lenz O, Loeliger C, Sakho M, Koulemou K, Koivogui L, Hoerauf A. Old and New World arenaviruses share a highly conserved epitope in the fusion domain of the glycoprotein 2, which is recognized by Lassa virus-specific human CD4+ T-cell clones. Virology. 2004;321:134–143. doi: 10.1016/j.virol.2003.12.013. [DOI] [PubMed] [Google Scholar]
  78. Meyer BJ, de la Torre JC, Southern PJ. Arenaviruses: genomic RNAs, transcription, and replication. Curr Top Microbiol Immunol. 2002;262:139–157. doi: 10.1007/978-3-642-56029-3_6. [DOI] [PubMed] [Google Scholar]
  79. Mouquet H, Scharf L, Euler Z, Liu Y, Eden C, Scheid JF, Halper-Stromberg A, Gnanapragasam PN, Spencer DI, Seaman MS, Schuitemaker H, Feizi T, Nussenzweig MC, Bjorkman PJ. Complex-type N-glycan recognition by potent broadly neutralizing HIV antibodies. Proc Natl Acad Sci U S A. 2012;109:E3268–3277. doi: 10.1073/pnas.1217207109. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Ngo N, Cubitt B, Iwasaki M, de la Torre JC. Identification and Mechanism of Action of a Novel Small-Molecule Inhibitor of Arenavirus Multiplication. J Virol. 2015;89:10924–10933. doi: 10.1128/JVI.01587-15. [DOI] [PMC free article] [PubMed] [Google Scholar] [Retracted]
  81. Oldstone MB. A suspenseful game of 'hide and seek' between virus and host. Nat Immunol. 2007;8:325–327. doi: 10.1038/ni0407-325. [DOI] [PubMed] [Google Scholar]
  82. Parsy ML, Harlos K, Huiskonen JT, Bowden TA. Crystal structure of Venezuelan hemorrhagic fever virus fusion glycoprotein reveals a class 1 postfusion architecture with extensive glycosylation. J Virol. 2013;87:13070–13075. doi: 10.1128/JVI.02298-13. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Pasqual G, Rojek JM, Masin M, Chatton JY, Kunz S. Old world arenaviruses enter the host cell via the multivesicular body and depend on the endosomal sorting complex required for transport. PLoS Pathog. 2011;7:e1002232. doi: 10.1371/journal.ppat.1002232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Pasquato A, Burri DJ, Traba E H-, El-Daher L, Seidah NG, Kunz S. Arenavirus envelope glycoproteins mimic autoprocessing sites of the cellular proprotein convertase subtilisin kexin isozyme-1/site-1 protease. Virology. 2011;417:18–26. doi: 10.1016/j.virol.2011.04.021. [DOI] [PubMed] [Google Scholar]
  85. Pejchal R, Doores KJ, Walker LM, Khayat R, Huang PS, Wang SK, Stanfield RL, Julien JP, Ramos A, Crispin M, Depetris R, Katpally U, Marozsan A, Cupo A, Maloveste S, Liu Y, McBride R, Ito Y, Sanders RW, Ogohara C, Paulson JC, Feizi T, Scanlan CN, Wong CH, Moore JP, Olson WC, Ward AB, Poignard P, Schief WR, Burton DR, Wilson IA. A potent and broad neutralizing antibody recognizes and penetrates the HIV glycan shield. Science. 2011;334:1097–1103. doi: 10.1126/science.1213256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  86. Perez M, Craven RC, de la Torre JC. The small RING finger protein Z drives arenavirus budding: implications for antiviral strategies. Proc Natl Acad Sci U S A. 2003;100:12978–12983. doi: 10.1073/pnas.2133782100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  87. Pinschewer DD, Perez M, de la Torre JC. Role of the virus nucleoprotein in the regulation of lymphocytic choriomeningitis virus transcription and RNA replication. J Virol. 2003;77:3882–3887. doi: 10.1128/JVI.77.6.3882-3887.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  88. Pushko P, Geisbert J, Parker M, Jahrling P, Smith J. Individual and bivalent vaccines based on alphavirus replicons protect guinea pigs against infection with Lassa and Ebola viruses. J Virol. 2001;75:11677–11685. doi: 10.1128/JVI.75.23.11677-11685.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  89. Quirin K, Eschli B, Scheu I, Poort L, Kartenbeck J, Helenius A. Lymphocytic choriomeningitis virus uses a novel endocytic pathway for infectious entry via late endosomes. Virology. 2008;378:21–33. doi: 10.1016/j.virol.2008.04.046. [DOI] [PubMed] [Google Scholar]
  90. Radoshitzky SR, Abraham J, Spiropoulou CF, Kuhn JH, Nguyen D, Li W, Nagel J, Schmidt PJ, Nunberg JH, Andrews NC, Farzan M, Choe H. Transferrin receptor 1 is a cellular receptor for New World haemorrhagic fever arenaviruses. Nature. 2007;446:92–96. doi: 10.1038/nature05539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  91. Radoshitzky SR, Bao Y, Buchmeier MJ, Charrel RN, Clawson AN, Clegg C D, Risi JL, Emonet S, Gonzalez JP, Kuhn JH, Lukashevich IS, Peters CJ, Romanowski V, Salvato MS, Stenglein MD, de la Torre JC. Past, present, and future of arenavirus taxonomy. Arch Virol. 2015;160:1851–1874. doi: 10.1007/s00705-015-2418-y. [DOI] [PubMed] [Google Scholar]
  92. Radoshitzky SR, Longobardi LE, Kuhn JH, Retterer C, Dong L, Clester JC, Kota K, Carra J, Bavari S. Machupo virus glycoprotein determinants for human transferrin receptor 1 binding and cell entry. PLoS One. 2011;6:e21398. doi: 10.1371/journal.pone.0021398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  93. Robert X, Gouet P. Deciphering key features in protein structures with the new ENDscript server. Nucleic Acids Res. 2014;42:W320–W324. doi: 10.1093/nar/gku316. [DOI] [PMC free article] [PubMed] [Google Scholar]
  94. Robinson JE, Hastie KM, Cross RW, Yenni RE, Elliott DH, Rouelle JA, Kannadka CB, Smira AA, Garry CE, Bradley BT, Yu H, Shaffer JG, Boisen ML, Hartnett JN, Zandonatti MA, Rowland MM, Heinrich ML, Martinez-Sobrido L, Cheng B, de la Torre JC, Andersen KG, Goba A, Momoh M, Fullah M, Gbakie M, Kanneh L, Koroma VJ, Fonnie R, Jalloh SC, Kargbo B, Vandi MA, Gbetuwa M, Ikponmwosa O, Asogun DA, Okokhere PO, Follarin OA, Schieffelin JS, Pitts KR, Geisbert JB, Kulakoski PC, Wilson RB, Happi CT, Sabeti PC, Gevao SM, Khan SH, Grant DS, Geisbert TW, Saphire EO, Branco LM, Garry RF. Most neutralizing human monoclonal antibodies target novel epitopes requiring both Lassa virus glycoprotein subunits. Nat Commun. 2016;7:11544. doi: 10.1038/ncomms11544. [DOI] [PMC free article] [PubMed] [Google Scholar]
  95. Rojek JM, Campbell KP, Oldstone MB, Kunz S. Old World arenavirus infection interferes with the expression of functional alpha-dystroglycan in the host cell. Mol Biol Cell. 2007;18:4493–4507. doi: 10.1091/mbc.E07-04-0374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  96. Rojek JM, Kunz S. Cell entry by human pathogenic arenaviruses. Cell Microbiol. 2008;10:828–835. doi: 10.1111/j.1462-5822.2007.01113.x. [DOI] [PubMed] [Google Scholar]
  97. Rojek JM, Lee AM, Nguyen N, Spiropoulou CF, Kunz S. Site 1 protease is required for proteolytic processing of the glycoproteins of the South American hemorrhagic fever viruses Junin, Machupo, and Guanarito. J Virol. 2008;82:6045–6051. doi: 10.1128/JVI.02392-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
  98. Rojek JM, Sanchez AB, Nguyen NT, de la Torre JC, Kunz S. Different mechanisms of cell entry by human-pathogenic Old World and New World arenaviruses. J Virol. 2008;82:7677–7687. doi: 10.1128/JVI.00560-08. [DOI] [PMC free article] [PubMed] [Google Scholar]
  99. Rojek JM, Spiropoulou CF, Campbell KP, Kunz S. Old World and clade C New World arenaviruses mimic the molecular mechanism of receptor recognition used by alpha-dystroglycan's host-derived ligands. J Virol. 2007;81:5685–5695. doi: 10.1128/JVI.02574-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  100. Salvato MS, Clegg JCS, Buchmeier MJ, Charrel RN, Gonzalez JP, Lukashevich IS, Peters CJ, Rico-Hesse R, Romanowski V. Family Arenaviridae. In: Van Regenmortel MHV, Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball LA, editors. Virus Taxonomy, Eighth report of the International Committee on Taxonomy of Viruses. Cambridge: Academic Press; 2005. [Google Scholar]
  101. Salvato MS, Schweighofer KJ, Burns J, Shimomaye EM. Biochemical and immunological evidence that the 11 kDa zinc-binding protein of lymphocytic choriomeningitis virus is a structural component of the virus. Virus Res. 1992;22:185–198. doi: 10.1016/0168-1702(92)90050-J. [DOI] [PubMed] [Google Scholar]
  102. Salvato MS, Shimomaye EM. The completed sequence of lymphocytic choriomeningitis virus reveals a unique RNA structure and a gene for a zinc finger protein. Virology. 1989;173:1–10. doi: 10.1016/0042-6822(89)90216-X. [DOI] [PubMed] [Google Scholar]
  103. Saunders AA, Ting JP, Meisner J, Neuman BW, Perez M, de la Torre JC, Buchmeier MJ. Mapping the landscape of the lymphocytic choriomeningitis virus stable signal peptide reveals novel functional domains. J Virol. 2007;81:5649–5657. doi: 10.1128/JVI.02759-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  104. Schmitt AP, Leser GP, Morita E, Sundquist WI, Lamb RA. Evidence for a new viral late-domain core sequence, FPIV, necessary for budding of a paramyxovirus. J Virol. 2005;79:2988–2997. doi: 10.1128/JVI.79.5.2988-2997.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  105. Schrempf S, Froeschke M, Giroglou T v, Laer D, Dobberstein B. Signal peptide requirements for lymphocytic choriomeningitis virus glycoprotein C maturation and virus infectivity. J Virol. 2007;81:12515–12524. doi: 10.1128/JVI.01481-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
  106. Schwarz F, Aebi M. Mechanisms and principles of N-linked protein glycosylation. Curr Opin Struct Biol. 2011;21:576–582. doi: 10.1016/j.sbi.2011.08.005. [DOI] [PubMed] [Google Scholar]
  107. Seregin AV, Yun NE, Miller M, Aronson J, Smith JK, Walker AG, Smith JN, Huang C, Manning JT, de la Torre JC, Paessler S. The glycoprotein precursor gene of Junin virus determines the virulence of the Romero strain and the attenuation of the Candid #1 strain in a representative animal model of Argentine hemorrhagic fever. J Virol. 2015;89:5949–5956. doi: 10.1128/JVI.00104-15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  108. Shimojima M, Kawaoka Y. Cell Surface Molecules Involved in Infection Mediated by Lymphocytic Choriomeningitis Virus Glycoprotein. J Vet Med Sci. 2012;74:1363–1366. doi: 10.1292/jvms.12-0176. [DOI] [PMC free article] [PubMed] [Google Scholar]
  109. Shimojima M, Stroher U, Ebihara H, Feldmann H, Kawaoka Y. Identification of cell surface molecules involved in dystroglycan-independent Lassa virus cell entry. J Virol. 2012;86:2067–2078. doi: 10.1128/JVI.06451-11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  110. Sommerstein R, Flatz L, Remy MM, Malinge P, Magistrelli G, Fischer N, Sahin M, Bergthaler A, Igonet S T, Meulen J, Rigo D, Meda P, Rabah N, Coutard B, Bowden TA, Lambert PH, Siegrist CA, Pinschewer DD. Arenavirus Glycan Shield Promotes Neutralizing Antibody Evasion and Protracted Infection. PLoS Pathog. 2015;11:e1005276. doi: 10.1371/journal.ppat.1005276. [DOI] [PMC free article] [PubMed] [Google Scholar]
  111. Spence JS, Melnik LI, Badani H, Wimley WC, Garry RF. Inhibition of arenavirus infection by a glycoprotein-derived peptide with a novel mechanism. J Virol. 2014;88:8556–8564. doi: 10.1128/JVI.01133-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  112. Strecker T, Eichler R, Meulen J, Weissenhorn W D, Klenk H, Garten W, Lenz O. Lassa virus Z protein is a matrix protein and sufficient for the release of virus-like particles [corrected] J Virol. 2003;77:10700–10705. doi: 10.1128/JVI.77.19.10700-10705.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  113. Tani H, Iha K, Shimojima M, Fukushi S, Taniguchi S, Yoshikawa T, Kawaoka Y, Nakasone N, Ninomiya H, Saijo M, Morikawa S. Analysis of Lujo virus cell entry using pseudotype vesicular stomatitis virus. J Virol. 2014;88:7317–7330. doi: 10.1128/JVI.00512-14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  114. ter Meulen J, Badusche M, Kuhnt K, Doetze A, Satoguina J, Marti T, Loeliger C, Koulemou K, Koivogui L, Schmitz H, Fleischer B, Hoerauf A. Characterization of human CD4(+) T-cell clones recognizing conserved and variable epitopes of the Lassa virus nucleoprotein. J Virol. 2000;74:2186–2192. doi: 10.1128/JVI.74.5.2186-2192.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  115. Vela EM, Zhang L, Colpitts TM, Davey RA, Aronson JF. Arenavirus entry occurs through a cholesterol-dependent, non-caveolar, clathrin-mediated endocytic mechanism. Virology. 2007;369:1–11. doi: 10.1016/j.virol.2007.07.014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  116. Walker LM, Huber M, Doores KJ, Falkowska E, Pejchal R, Julien JP, Wang SK, Ramos A, Chan-Hui PY, Moyle M, Mitcham JL, Hammond PW, Olsen OA, Phung P, Fling S, Wong CH, Phogat S, Wrin T, Simek MD, Protocol GPI, Koff WC, Wilson IA, Burton DR, Poignard P. Broad neutralization coverage of HIV by multiple highly potent antibodies. Nature. 2011;477:466–470. doi: 10.1038/nature10373. [DOI] [PMC free article] [PubMed] [Google Scholar]
  117. Weber EL, Buchmeier MJ. Fine mapping of a peptide sequence containing an antigenic site conserved among arenaviruses. Virology. 1988;164:30–38. doi: 10.1016/0042-6822(88)90616-2. [DOI] [PubMed] [Google Scholar]
  118. Wright KE, Salvato MS, Buchmeier MJ. Neutralizing epitopes of lymphocytic choriomeningitis virus are conformational and require both glycosylation and disulfide bonds for expression. Virology. 1989;171:417–426. doi: 10.1016/0042-6822(89)90610-7. [DOI] [PubMed] [Google Scholar]
  119. Yamamoto T, Kato Y, Karita M, Kawaguchi M, Shibata N, Kobayashi M. Expression of genes related to muscular dystrophy with lissencephaly. Pediatr Neurol. 2004;31:183–190. doi: 10.1016/j.pediatrneurol.2004.03.020. [DOI] [PubMed] [Google Scholar]
  120. York J, Agnihothram SS, Romanowski V, Nunberg JH. Genetic analysis of heptad-repeat regions in the G2 fusion subunit of the Junin arenavirus envelope glycoprotein. Virology. 2005;343:267–274. doi: 10.1016/j.virol.2005.08.030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  121. York J, Dai D, Amberg SM, Nunberg JH. pH-induced activation of arenavirus membrane fusion is antagonized by small-molecule inhibitors. J Virol. 2008;82:10932–10939. doi: 10.1128/JVI.01140-08. [DOI] [PMC free article] [PubMed] [Google Scholar]
  122. York J, Nunberg JH. Role of the stable signal peptide of Junin arenavirus envelope glycoprotein in pH-dependent membrane fusion. J Virol. 2006;80:7775–7780. doi: 10.1128/JVI.00642-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  123. York J, Nunberg JH. Distinct requirements for signal peptidase processing and function in the stable signal peptide subunit of the Junin virus envelope glycoprotein. Virology. 2007;359:72–81. doi: 10.1016/j.virol.2006.08.048. [DOI] [PubMed] [Google Scholar]
  124. York J, Nunberg JH. A novel zinc-binding domain is essential for formation of the functional Junin virus envelope glycoprotein complex. J Virol. 2007;81:13385–13391. doi: 10.1128/JVI.01785-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
  125. York J, Nunberg JH. Intersubunit interactions modulate pHinduced activation of membrane fusion by the Junin virus envelope glycoprotein GPC. J Virol. 2009;83:4121–4126. doi: 10.1128/JVI.02410-08. [DOI] [PMC free article] [PubMed] [Google Scholar]
  126. York J, Romanowski V, Lu M, Nunberg JH. The signal peptide of the Junin arenavirus envelope glycoprotein is myristoylated and forms an essential subunit of the mature G1-G2 complex. J Virol. 2004;78:10783–10792. doi: 10.1128/JVI.78.19.10783-10792.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  127. Young PR, Howard CR. Fine structure analysis of Pichinde virus nucleocapsids. J Gen Virol. 1983;64:833–842. doi: 10.1099/0022-1317-64-4-833. [DOI] [PubMed] [Google Scholar]

Articles from Virologica Sinica are provided here courtesy of Wuhan Institute of Virology, Chinese Academy of Sciences

RESOURCES