메뉴 건너뛰기




Volumn 312, Issue 2, 2003, Pages 395-406

The glycosylation status of the murine hepatitis coronavirus M protein affects the interferogenic capacity of the virus in vitro and its ability to replicate in the liver but not the brain

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERFERON; CARBOHYDRATE; HEPATITIS CORONAVIRUS M PROTEIN; MANNOSE RECEPTOR; OLIGOSACCHARIDE; UNCLASSIFIED DRUG; VIRUS PROTEIN;

EID: 0042062360     PISSN: 00426822     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0042-6822(03)00235-6     Document Type: Article
Times cited : (71)

References (56)
  • 1
    • 0021683576 scopus 로고
    • Carbohydrate dramatically influences immune reactivity of antisera to viral glycoprotein antigens
    • Alexander S., Elder J.H. Carbohydrate dramatically influences immune reactivity of antisera to viral glycoprotein antigens. Science. 226:1984;1328-1330.
    • (1984) Science , vol.226 , pp. 1328-1330
    • Alexander, S.1    Elder, J.H.2
  • 4
    • 0031713686 scopus 로고    scopus 로고
    • Coronavirus pseudoparticles formed with recombinant M and E proteins induce alpha interferon synthesis by leukocytes
    • Baudoux P., Carrat C., Besnardeau L., Charley B., Laude H. Coronavirus pseudoparticles formed with recombinant M and E proteins induce alpha interferon synthesis by leukocytes. J. Virol. 72:1998;8636-8643.
    • (1998) J. Virol. , vol.72 , pp. 8636-8643
    • Baudoux, P.1    Carrat, C.2    Besnardeau, L.3    Charley, B.4    Laude, H.5
  • 5
    • 0034231849 scopus 로고    scopus 로고
    • Folding of viral envelope glycoproteins in the endoplasmic reticulum
    • Braakman I., van Anken E. Folding of viral envelope glycoproteins in the endoplasmic reticulum. Traffic. 1:2000;533-539.
    • (2000) Traffic , vol.1 , pp. 533-539
    • Braakman, I.1    Van Anken, E.2
  • 6
    • 0023905741 scopus 로고
    • Induction of alpha interferon by transmissible gastroenteritis coronavirus: Role of transmembrane glycoprotein E1
    • Charley B., Laude H. Induction of alpha interferon by transmissible gastroenteritis coronavirus role of transmembrane glycoprotein E1 . J. Virol. 62:1988;8-11.
    • (1988) J. Virol. , vol.62 , pp. 8-11
    • Charley, B.1    Laude, H.2
  • 7
    • 0028001582 scopus 로고
    • Enterotropic strains of mouse coronavirus differ in their use of murine carcinoembryonic antigen-related glycoprotein receptors
    • doi:10.1006/viro.1994.1475
    • Compton S.R. Enterotropic strains of mouse coronavirus differ in their use of murine carcinoembryonic antigen-related glycoprotein receptors. Virology. 203:1994;197-201. doi:10.1006/viro.1994.1475.
    • (1994) Virology , vol.203 , pp. 197-201
    • Compton, S.R.1
  • 9
    • 0034067478 scopus 로고    scopus 로고
    • Assembly of the coronavirus envelope: Homotypic interactions between the M proteins
    • de Haan C.A.M., Vennema H., Rottier P.J.M. Assembly of the coronavirus envelope homotypic interactions between the M proteins . J. Virol. 74:2000;4967-4978.
    • (2000) J. Virol. , vol.74 , pp. 4967-4978
    • De Haan, C.A.M.1    Vennema, H.2    Rottier, P.J.M.3
  • 10
    • 0031950008 scopus 로고    scopus 로고
    • Coronavirus particle assembly: Primary structure requirements of the membrane protein
    • de Haan C.A.M., Kuo L., Masters P.S., Vennema H., Rottier P.J.M. Coronavirus particle assembly primary structure requirements of the membrane protein . J. Virol. 72:1998;6838-6850.
    • (1998) J. Virol. , vol.72 , pp. 6838-6850
    • De Haan, C.A.M.1    Kuo, L.2    Masters, P.S.3    Vennema, H.4    Rottier, P.J.M.5
  • 12
    • 0032874344 scopus 로고    scopus 로고
    • Mapping of the coronavirus membrane protein domains involved in interaction with the spike protein
    • de Haan C.A.M., Smeets M., Vernooij F., Vennema H., Rottier P.J.M. Mapping of the coronavirus membrane protein domains involved in interaction with the spike protein. J. Virol. 73:1999;7441-7452.
    • (1999) J. Virol. , vol.73 , pp. 7441-7452
    • De Haan, C.A.M.1    Smeets, M.2    Vernooij, F.3    Vennema, H.4    Rottier, P.J.M.5
  • 13
    • 0025103827 scopus 로고
    • Assembly of coronavirus spike protein into trimers and its role in epitope expression
    • Delmas B., Laude H. Assembly of coronavirus spike protein into trimers and its role in epitope expression. J. Virol. 64:1990;5367-5375.
    • (1990) J. Virol. , vol.64 , pp. 5367-5375
    • Delmas, B.1    Laude, H.2
  • 14
    • 0032168441 scopus 로고    scopus 로고
    • Evolving views of protein glycosylation
    • Drickamer K., Taylor M.E. Evolving views of protein glycosylation. Trends Biochem. Sci. 23:1998;321-324.
    • (1998) Trends Biochem. Sci. , vol.23 , pp. 321-324
    • Drickamer, K.1    Taylor, M.E.2
  • 15
    • 0031010131 scopus 로고    scopus 로고
    • Analysis of a recombinant mouse hepatitis virus expressing a foreign gene reveals a novel aspect of coronavirus transcription
    • Fischer F., Stegen C.F., Koetzner C.A., Masters P.S. Analysis of a recombinant mouse hepatitis virus expressing a foreign gene reveals a novel aspect of coronavirus transcription. J. Virol. 71:1997;5148-5160.
    • (1997) J. Virol. , vol.71 , pp. 5148-5160
    • Fischer, F.1    Stegen, C.F.2    Koetzner, C.A.3    Masters, P.S.4
  • 16
    • 0027788005 scopus 로고
    • Human natural interferon-alpha producing cells
    • Fitzgerald-Bocarsly P. Human natural interferon-alpha producing cells. Pharmacol. Ther. 60:1993;39-62.
    • (1993) Pharmacol. Ther. , vol.60 , pp. 39-62
    • Fitzgerald-Bocarsly, P.1
  • 17
    • 0033960161 scopus 로고    scopus 로고
    • Assembly of spikes into coronavirus particles is mediated by the carboxy-terminal domain of the spike protein
    • Godeke G.J., de Haan C.A.M., Rossen J.W., Vennema H., Rottier P.J.M. Assembly of spikes into coronavirus particles is mediated by the carboxy-terminal domain of the spike protein. J. Virol. 74:2000;1566-1571.
    • (2000) J. Virol. , vol.74 , pp. 1566-1571
    • Godeke, G.J.1    De Haan, C.A.M.2    Rossen, J.W.3    Vennema, H.4    Rottier, P.J.M.5
  • 18
    • 0035937505 scopus 로고    scopus 로고
    • Intracellular functions of N-linked glycans
    • Helenius A., Aebi M. Intracellular functions of N-linked glycans. Science. 291:2001;2364-2369.
    • (2001) Science , vol.291 , pp. 2364-2369
    • Helenius, A.1    Aebi, M.2
  • 19
    • 0028222194 scopus 로고
    • MHV-A59 fusion mutants are attenuated and display altered hepatotropism
    • doi:10.1006/viro.1994.1156
    • Hingley S.T., Gombold J.L., Lavi E., Weiss S.R. MHV-A59 fusion mutants are attenuated and display altered hepatotropism. Virology. 200:1994;1-10. doi:10.1006/viro.1994.1156.
    • (1994) Virology , vol.200 , pp. 1-10
    • Hingley, S.T.1    Gombold, J.L.2    Lavi, E.3    Weiss, S.R.4
  • 20
    • 0019845221 scopus 로고
    • Tunicamycin resistant glycosylation of coronavirus glycoprotein: Demonstration of a novel type of viral glycoprotein
    • Holmes K.V., Doller E.W., Sturman L.S. Tunicamycin resistant glycosylation of coronavirus glycoprotein demonstration of a novel type of viral glycoprotein . Virology. 115:1981;334-344.
    • (1981) Virology , vol.115 , pp. 334-344
    • Holmes, K.V.1    Doller, E.W.2    Sturman, L.S.3
  • 21
    • 0028105726 scopus 로고
    • Induction of interferon by virus glycoprtein(s) in lymphoid cells through interaction with the cellular receptors via lectin-like action: An alternative interferon induction mechanism
    • Ito Y. Induction of interferon by virus glycoprtein(s) in lymphoid cells through interaction with the cellular receptors via lectin-like action an alternative interferon induction mechanism . Arch. Virol. 138:1994;187-198.
    • (1994) Arch. Virol. , vol.138 , pp. 187-198
    • Ito, Y.1
  • 22
    • 0026691820 scopus 로고
    • O-glycosylation of the coronavirus M protein. Differential localization of sialyltransferases in N- and O-linked glycosylation
    • Krijnse Locker J., Griffiths G., Horzinek M.C., Rottier P.J.M. O-glycosylation of the coronavirus M protein. Differential localization of sialyltransferases in N- and O-linked glycosylation. J. Biol. Chem. 267:1992;14094-14101.
    • (1992) J. Biol. Chem. , vol.267 , pp. 14094-14101
    • Krijnse Locker, J.1    Griffiths, G.2    Horzinek, M.C.3    Rottier, P.J.M.4
  • 23
    • 0033982337 scopus 로고    scopus 로고
    • Retargeting of coronavirus by substitution of the spike glycoprotein ectodomain: Crossing the host cell species barrier
    • Kuo L., Godeke G.J., Raamsman M.J., Masters P.S., Rottier P.J.M. Retargeting of coronavirus by substitution of the spike glycoprotein ectodomain crossing the host cell species barrier . J. Virol. 74:2000;1393-1406.
    • (2000) J. Virol. , vol.74 , pp. 1393-1406
    • Kuo, L.1    Godeke, G.J.2    Raamsman, M.J.3    Masters, P.S.4    Rottier, P.J.M.5
  • 24
    • 0022494764 scopus 로고
    • Biological and antigenic relationships between virus-induced porcine and human interferons
    • La Bonnardiere C., Laude H., Berg K. Biological and antigenic relationships between virus-induced porcine and human interferons. Ann. Inst. Pasteur Virol. 137E:1986;171-180.
    • (1986) Ann. Inst. Pasteur Virol. , vol.137 E , pp. 171-180
    • La Bonnardiere, C.1    Laude, H.2    Berg, K.3
  • 25
    • 0026529211 scopus 로고
    • Single amino acid changes in the viral glycoprotein M affect induction of alpha interferon by the coronavirus transmissible gastroenteritis virus
    • Laude H., Gelfi J., Lavenant L., Charley B. Single amino acid changes in the viral glycoprotein M affect induction of alpha interferon by the coronavirus transmissible gastroenteritis virus. J. Virol. 66:1992;743-749.
    • (1992) J. Virol. , vol.66 , pp. 743-749
    • Laude, H.1    Gelfi, J.2    Lavenant, L.3    Charley, B.4
  • 27
    • 0033258372 scopus 로고    scopus 로고
    • Reverse genetics of the largest RNA viruses
    • Masters P.S. Reverse genetics of the largest RNA viruses. Adv. Virus Res. 53:1999;245-264.
    • (1999) Adv. Virus Res. , vol.53 , pp. 245-264
    • Masters, P.S.1
  • 28
    • 0028091057 scopus 로고
    • Optimization of targeted RNA recombination and mapping of a novel nucleocapsid gene mutation in the coronavirus mouse hepatitis virus
    • Masters P.S., Koetzner C.A., Kerr C.A., Heo Y. Optimization of targeted RNA recombination and mapping of a novel nucleocapsid gene mutation in the coronavirus mouse hepatitis virus. J. Virol. 68:1994;328-337.
    • (1994) J. Virol. , vol.68 , pp. 328-337
    • Masters, P.S.1    Koetzner, C.A.2    Kerr, C.A.3    Heo, Y.4
  • 29
    • 0033829896 scopus 로고    scopus 로고
    • Protective effects of murine recombinant interferon-beta administered by intravenous, intramuscular or subcutaneous route on mouse hepatitis virus infection
    • Matsuyama S., Henmi S., Ichihara N., Sone S., Kikuchi T., Ariga T., Taguchi F. Protective effects of murine recombinant interferon-beta administered by intravenous, intramuscular or subcutaneous route on mouse hepatitis virus infection. Antiviral Res. 47:2000;131-137.
    • (2000) Antiviral Res. , vol.47 , pp. 131-137
    • Matsuyama, S.1    Henmi, S.2    Ichihara, N.3    Sone, S.4    Kikuchi, T.5    Ariga, T.6    Taguchi, F.7
  • 30
    • 0023807529 scopus 로고
    • Membrane integration and intracellular transport of the coronavirus glycoprotein E1, a class III membrane glycoprotein
    • Mayer T., Tamura T., Falk M., Niemann H. Membrane integration and intracellular transport of the coronavirus glycoprotein E1, a class III membrane glycoprotein. J. Biol. Chem. 263:1988;14956-14963.
    • (1988) J. Biol. Chem. , vol.263 , pp. 14956-14963
    • Mayer, T.1    Tamura, T.2    Falk, M.3    Niemann, H.4
  • 31
    • 0032168556 scopus 로고    scopus 로고
    • The mannose receptor mediates induction of IFN-alpha in peripheral blood dendritic cells by enveloped RNA and DNA viruses
    • Milone M.C., Fitzgerald-Bocarsly P. The mannose receptor mediates induction of IFN-alpha in peripheral blood dendritic cells by enveloped RNA and DNA viruses. J. Immunol. 161:1998;2391-2399.
    • (1998) J. Immunol. , vol.161 , pp. 2391-2399
    • Milone, M.C.1    Fitzgerald-Bocarsly, P.2
  • 33
    • 0033899980 scopus 로고    scopus 로고
    • Characterization of the coronavirus M protein and nucleocapsid interaction in infected cells
    • Narayanan K., Maeda A., Maeda J., Makino S. Characterization of the coronavirus M protein and nucleocapsid interaction in infected cells. J. Virol. 74:2000;8127-8134.
    • (2000) J. Virol. , vol.74 , pp. 8127-8134
    • Narayanan, K.1    Maeda, A.2    Maeda, J.3    Makino, S.4
  • 34
    • 0035127581 scopus 로고    scopus 로고
    • Murine coronavirus spike protein determines the ability of the virus to replicate in the liver and cause hepatitis
    • Navas S., Seo S.H., Chua M.M., Sarma J.D., Lavi E., Hingley S.T., Weiss S.R. Murine coronavirus spike protein determines the ability of the virus to replicate in the liver and cause hepatitis. J. Virol. 75:2001;2452-2457.
    • (2001) J. Virol. , vol.75 , pp. 2452-2457
    • Navas, S.1    Seo, S.H.2    Chua, M.M.3    Sarma, J.D.4    Lavi, E.5    Hingley, S.T.6    Weiss, S.R.7
  • 35
    • 0030782149 scopus 로고    scopus 로고
    • Protein interactions during coronavirus assembly
    • Nguyen V.P., Hogue B.G. Protein interactions during coronavirus assembly. J. Virol. 71:1997;9278-9284.
    • (1997) J. Virol. , vol.71 , pp. 9278-9284
    • Nguyen, V.P.1    Hogue, B.G.2
  • 36
    • 0020339971 scopus 로고
    • Post-translational glycosylation of coronavirus glycoprotein E1: Inhibition by monensin
    • Niemann H., Boschek B., Evans D., Rosing M., Tamura T., Klenk H.-D. Post-translational glycosylation of coronavirus glycoprotein E1 inhibition by monensin . EMBO J. 1:1982;1499-1504.
    • (1982) EMBO J. , vol.1 , pp. 1499-1504
    • Niemann, H.1    Boschek, B.2    Evans, D.3    Rosing, M.4    Tamura, T.5    Klenk, H.-D.6
  • 38
    • 0029117953 scopus 로고
    • Construction of murine coronavirus mutants containing interspecies chimeric nucleocapsid proteins
    • Peng D., Koetzner C.A., McMahon T., Zhu Y., Masters P.S. Construction of murine coronavirus mutants containing interspecies chimeric nucleocapsid proteins. J. Virol. 69:1995;5475-5484.
    • (1995) J. Virol. , vol.69 , pp. 5475-5484
    • Peng, D.1    Koetzner, C.A.2    McMahon, T.3    Zhu, Y.4    Masters, P.S.5
  • 39
    • 33745158157 scopus 로고
    • A simple method of estimating fifty percent points
    • Reed L.J., Muench H. A simple method of estimating fifty percent points. Am. J. Hygeine. 27:1938;493-497.
    • (1938) Am. J. Hygeine , vol.27 , pp. 493-497
    • Reed, L.J.1    Muench, H.2
  • 41
    • 0030273298 scopus 로고    scopus 로고
    • A murine and a porcine coronavirus are released from opposite surfaces of the same epithelial cells
    • doi:10.1006/viro.1996.0540
    • Rossen J.W.A., Bekker C.P.J., Strous G.J.A.M., Horzinek M.C., Dveksler G.S., Holmes K.V., Rottier P.J.M. A murine and a porcine coronavirus are released from opposite surfaces of the same epithelial cells. Virology. 224:1996;345-351. doi:10.1006/viro.1996.0540.
    • (1996) Virology , vol.224 , pp. 345-351
    • Rossen, J.W.A.1    Bekker, C.P.J.2    Strous, G.J.A.M.3    Horzinek, M.C.4    Dveksler, G.S.5    Holmes, K.V.6    Rottier, P.J.M.7
  • 42
    • 0019850652 scopus 로고
    • Viral protein synthesis in mouse hepatitis virus strain A59-infected cells: Effect of tunicamycin
    • Rottier P.J.M., Horzinek M.C., van der Zeijst B.A. Viral protein synthesis in mouse hepatitis virus strain A59-infected cells effect of tunicamycin . J. Virol. 40:1981;350-357.
    • (1981) J. Virol. , vol.40 , pp. 350-357
    • Rottier, P.J.M.1    Horzinek, M.C.2    Van Der Zeijst, B.A.3
  • 43
    • 0002753706 scopus 로고
    • The coronavirus membrane protein
    • S.G. Siddell. New York: Plenum Press
    • Rottier P.J.M. The coronavirus membrane protein. Siddell S.G. The Coronaviridae. 1995;115-139 Plenum Press, New York.
    • (1995) The Coronaviridae , pp. 115-139
    • Rottier, P.J.M.1
  • 44
    • 0025541806 scopus 로고
    • Expression of MHV-A59 M glycoprotein: Effects of deletions on membrane integration and intracellular transport
    • Rottier P.J.M., Krijnse Locker J., Horzinek M.C., Spaan W.J.M. Expression of MHV-A59 M glycoprotein effects of deletions on membrane integration and intracellular transport . Adv. Exp. Med. Biol. 276:1990;127-135.
    • (1990) Adv. Exp. Med. Biol. , vol.276 , pp. 127-135
    • Rottier, P.J.M.1    Krijnse Locker, J.2    Horzinek, M.C.3    Spaan, W.J.M.4
  • 45
    • 0030937062 scopus 로고    scopus 로고
    • Glycosylation: Heterogeneity and the 3D structure of proteins
    • Rudd P.M., Dwek R.A. Glycosylation heterogeneity and the 3D structure of proteins . Crit. Rev. Biochem. Mol. Biol. 32:1997;1-100.
    • (1997) Crit. Rev. Biochem. Mol. Biol. , vol.32 , pp. 1-100
    • Rudd, P.M.1    Dwek, R.A.2
  • 46
    • 0030740376 scopus 로고    scopus 로고
    • Effects of glycosylation on the properties and functions of influenza virus hemagglutinin
    • Schulze I.T. Effects of glycosylation on the properties and functions of influenza virus hemagglutinin. J. Infect. Dis. 176:(Suppl 1):1997;S24-S28.
    • (1997) J. Infect. Dis. , vol.176 , Issue.SUPPL. 1
    • Schulze, I.T.1
  • 48
    • 0023544356 scopus 로고
    • Intranasally administered alpha/beta interferon prevents extension of mouse hepatitis virus, strain JHM, into the brains of BALB/cByJ mice
    • Smith A.L., Barthold S.W., Beck D.S. Intranasally administered alpha/beta interferon prevents extension of mouse hepatitis virus, strain JHM, into the brains of BALB/cByJ mice. Antiviral Res. 8:1987;239-245.
    • (1987) Antiviral Res. , vol.8 , pp. 239-245
    • Smith, A.L.1    Barthold, S.W.2    Beck, D.S.3
  • 49
    • 0032005288 scopus 로고    scopus 로고
    • The mannose receptor is a pattern recognition receptor involved in host defense
    • Stahl P.D., Ezekowitz R.A. The mannose receptor is a pattern recognition receptor involved in host defense. Curr. Opin. Immunol. 10:1998;50-55.
    • (1998) Curr. Opin. Immunol. , vol.10 , pp. 50-55
    • Stahl, P.D.1    Ezekowitz, R.A.2
  • 50
    • 0020423602 scopus 로고
    • Coronavirus proteins: Structure and function of the oligosaccharides of the avian infectious bronchitis virus glycoproteins
    • Stern D.F., Sefton B.M. Coronavirus proteins structure and function of the oligosaccharides of the avian infectious bronchitis virus glycoproteins . J. Virol. 44:1982;804-812.
    • (1982) J. Virol. , vol.44 , pp. 804-812
    • Stern, D.F.1    Sefton, B.M.2
  • 51
    • 0023916548 scopus 로고
    • Site of addition of N-acetyl-galactosamine to the E1 glycoprotein of mouse hepatitis virus-A59
    • Tooze S.A., Tooze J., Warren G. Site of addition of N-acetyl-galactosamine to the E1 glycoprotein of mouse hepatitis virus-A59. J. Cell Biol. 106:1988;1475-1487.
    • (1988) J. Cell Biol. , vol.106 , pp. 1475-1487
    • Tooze, S.A.1    Tooze, J.2    Warren, G.3
  • 52
    • 0030184599 scopus 로고    scopus 로고
    • Protective effect of recombinant interferon (IFN)-alpha/beta on MHV-2cc-induced chronic hepatitis in athymic nude mice
    • Uetsuka K., Nakayama H., Goto N. Protective effect of recombinant interferon (IFN)-alpha/beta on MHV-2cc-induced chronic hepatitis in athymic nude mice. Exp. Anim. 45:1996;293-297.
    • (1996) Exp. Anim. , vol.45 , pp. 293-297
    • Uetsuka, K.1    Nakayama, H.2    Goto, N.3
  • 54
    • 0029933250 scopus 로고    scopus 로고
    • Nucleocapsid-independent assembly of coronavirus-like particles by co-expression of viral envelope protein genes
    • Vennema H., Godeke G.J., Rossen J.W., Voorhout W.F., Horzinek M.C., Opstelten D.J., Rottier P.J.M. Nucleocapsid-independent assembly of coronavirus-like particles by co-expression of viral envelope protein genes. EMBO J. 15:1996;2020-2028.
    • (1996) EMBO J. , vol.15 , pp. 2020-2028
    • Vennema, H.1    Godeke, G.J.2    Rossen, J.W.3    Voorhout, W.F.4    Horzinek, M.C.5    Opstelten, D.J.6    Rottier, P.J.M.7
  • 55
    • 0025169833 scopus 로고
    • Intracellular transport of recombinant coronavirus spike proteins: Implications for virus assembly
    • Vennema H., Heijnen L., Zijderveld A., Horzinek M.C., Spaan W.J. Intracellular transport of recombinant coronavirus spike proteins implications for virus assembly . J. Virol. 64:1990;339-346.
    • (1990) J. Virol. , vol.64 , pp. 339-346
    • Vennema, H.1    Heijnen, L.2    Zijderveld, A.3    Horzinek, M.C.4    Spaan, W.J.5
  • 56
    • 0034052668 scopus 로고    scopus 로고
    • Unique N-linked glycosylation of murine coronavirus MHV-2 membrane protein at the conserved O-linked glycosylation site
    • Yamada Y.K., Yabe M., Ohtsuki T., Taguchi F. Unique N-linked glycosylation of murine coronavirus MHV-2 membrane protein at the conserved O-linked glycosylation site. Virus Res. 66:2000;149-154.
    • (2000) Virus Res. , vol.66 , pp. 149-154
    • Yamada, Y.K.1    Yabe, M.2    Ohtsuki, T.3    Taguchi, F.4


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.