ノロウイルスと血液型抗原
ノロウイルス(NoV)は世界各地で発生しているウイルス性下痢症の主たる原因ウイルスである.少なくとも33遺伝子型を有し,極めて多様性を持った集団として存在する.近年,NoVのプロトタイプであるNorwalk/68(NV/68)株が血液型抗原であるH(O),A,Leb型抗原に吸着することが明らかになった.血液型抗原とは抗原構造をもった糖鎖の総称であり,ヒトの赤血球表面だけでなく,NoVが標的とするであろう腸管上皮細胞にも発現されている.血液型抗原の合成に関与するフコース転位酵素の一つであるFUT2(Se)酵素をコードするFUT2遺伝子が活性型のヒトでは血液型抗原が腸管上皮細胞に発現されている(分...
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Published in | ウイルス Vol. 57; no. 2; pp. 181 - 189 |
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Main Authors | , |
Format | Journal Article |
Language | Japanese |
Published |
日本ウイルス学会
25.12.2007
|
Online Access | Get full text |
ISSN | 0042-6857 1884-3433 |
DOI | 10.2222/jsv.57.181 |
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Abstract | ノロウイルス(NoV)は世界各地で発生しているウイルス性下痢症の主たる原因ウイルスである.少なくとも33遺伝子型を有し,極めて多様性を持った集団として存在する.近年,NoVのプロトタイプであるNorwalk/68(NV/68)株が血液型抗原であるH(O),A,Leb型抗原に吸着することが明らかになった.血液型抗原とは抗原構造をもった糖鎖の総称であり,ヒトの赤血球表面だけでなく,NoVが標的とするであろう腸管上皮細胞にも発現されている.血液型抗原の合成に関与するフコース転位酵素の一つであるFUT2(Se)酵素をコードするFUT2遺伝子が活性型のヒトでは血液型抗原が腸管上皮細胞に発現されている(分泌型個体).これに対しSe遺伝子が変異により不活化すると,血液型抗原は上皮細胞に発現されなくなる(非分泌型個体).NV/68株をボランティアに感染させると分泌型個体で感染が成立し非分泌型個体では成立しない.さらに血液型間で感染率を比較検討すると,O型のヒトでの感染率が高くB型では感染率が低いことが報告されている.しかし,その一方でNoVに属するすべてのウイルス株がNV/68と同じ血液型抗原を認識するわけではないことが明らかになってきた.GII/4遺伝子型は他の遺伝子型に比べ結合できる血液型抗原の種類が多く,またそれぞれの血液型抗原への結合力も強いことがin vitro binding assay,疫学研究の両面から証明されている.この遺伝子型は,日本も含め世界中で流行している株であるが,その伝播力についても答えが出ていない.直接的な証明はまだなされていないものの,GII/4遺伝子型株の血液型抗原への結合力の強さが伝播力の強さに結びついている可能性が大きい.血液型抗原への吸着をスタートとしたNoVの感染が,その後,どの様なメカニズムによって下痢症発症にまで結びつくのか,解明が待たれる. |
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AbstractList | ノロウイルス(NoV)は世界各地で発生しているウイルス性下痢症の主たる原因ウイルスである.少なくとも33遺伝子型を有し,極めて多様性を持った集団として存在する.近年,NoVのプロトタイプであるNorwalk/68(NV/68)株が血液型抗原であるH(O),A,Leb型抗原に吸着することが明らかになった.血液型抗原とは抗原構造をもった糖鎖の総称であり,ヒトの赤血球表面だけでなく,NoVが標的とするであろう腸管上皮細胞にも発現されている.血液型抗原の合成に関与するフコース転位酵素の一つであるFUT2(Se)酵素をコードするFUT2遺伝子が活性型のヒトでは血液型抗原が腸管上皮細胞に発現されている(分泌型個体).これに対しSe遺伝子が変異により不活化すると,血液型抗原は上皮細胞に発現されなくなる(非分泌型個体).NV/68株をボランティアに感染させると分泌型個体で感染が成立し非分泌型個体では成立しない.さらに血液型間で感染率を比較検討すると,O型のヒトでの感染率が高くB型では感染率が低いことが報告されている.しかし,その一方でNoVに属するすべてのウイルス株がNV/68と同じ血液型抗原を認識するわけではないことが明らかになってきた.GII/4遺伝子型は他の遺伝子型に比べ結合できる血液型抗原の種類が多く,またそれぞれの血液型抗原への結合力も強いことがin vitro binding assay,疫学研究の両面から証明されている.この遺伝子型は,日本も含め世界中で流行している株であるが,その伝播力についても答えが出ていない.直接的な証明はまだなされていないものの,GII/4遺伝子型株の血液型抗原への結合力の強さが伝播力の強さに結びついている可能性が大きい.血液型抗原への吸着をスタートとしたNoVの感染が,その後,どの様なメカニズムによって下痢症発症にまで結びつくのか,解明が待たれる. |
Author | 武田, 直和 白土(堀越), 東子 |
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References | 7) Harrington, P. R., Vinjé J, Moe CL, Baric RS.: Norovirus capture with histo-blood group antigens reveals novel virus-ligand interactions. J. Virol. 78: 3035-3045, 2004. 15) Kageyama T, Shinohara M, Uchida K, Fukushi S, Hoshino FB, Kojima S, Takai R, Oka T, Takeda N, Katayama K. (2004) Coexistence of multiple genotypes, including newly identified genotypes, in outbreaks of gastroenteritis due to Norovirus in Japan. J. Clin. Microbiol. 42, 2988-2995 1) Cao, S., Lou, Z., Tan, M., Chen, Y., Liu, Y., Zhang, Z., Zhang, X. C., Jiang, X., Li, X., Rao, Z.: Structural Basis for the Recognition of Blood Group Trisaccharides by Norovirus. J. Virol. 81: 5949-5957, 2007. 16) Kaneko M, Nishihara S, Shinya N, Kudo T, Iwasaki H, Seno T, Okubo Y, Narimatsu H.: Free Full Text Wide variety of point mutations in the H gene of Bombay and para-Bombay individuals that inactivate H enzyme. Blood 90: 839-849, 1997. 17) Kudo T, Iwasaki H, Nishihara S, Shinya N, Ando T, Narimatsu I, Narimatsu H.: Molecular genetic analysis of the human Lewis histo-blood group system. II. Secretor gene inactivation by a novel single missense mutation A385T in Japanese nonsecretor individuals. J Biol Chem 271: 9830-9837, 1996. 11) Hutson AM, Atmar RL, Graham DY, Estes MK.: Norwalk virus infection and disease is associated with ABO histo-blood group type. J. Infect. Dis. 185: 1335-1337, 2002. 21) Okada M, Ogawa T, Kaiho I, Shinozaki K.: Genetic analysis of noroviruses in Chiba Prefecture, Japan, between 1999 and 2004. J. Clin. Microbiol. 43: 4391-4401, 2005. 3) Glass PJ, White LJ, Ball JM, Leparc-Goffart I, Hardy ME, Estes MK.: Norwalk virus open reading frame 3 encodes a minor structural protein. J. Virol. 74: 6581-6591, 2000. 20) Narimatsu H, Iwasaki H, Nakayama F, Ikehara Y, Kudo T, Nishihara S, Sugano K, Okura H, Fujita S, Hirohashi S.: Lewis and secretor gene dosages affect CA19-9 and DU-PAN-2 serum levels in normal individuals and colorectal cancer patients. Cancer Res. 58: 512-518, 1998. 23) Prasad, B. V. V., Hardy ME, Dokland T, Bella J, Rossmann MG, Estes MK.: X-ray crystallographic structure of the Norwalk virus capsid. Science 286: 287-290, 1999. 10) Hutson AM, Atmar RL, Estes MK.: Norovirus disease: changing epidemiology and host susceptibility factors. Trends Microbiol 12: 279-287, 2004. 5) Hansman GS, Natori K, Shirato-Horikoshi H, Ogawa S, Oka T, Katayama K, Tanaka T, Miyoshi T, Sakae K, Kobayashi S, Shinohara M, Uchida K, Sakurai N, Shinozaki K, Okada M, Seto Y, Kamata K, Nagata N, Tanaka K, Miyamura T, Takeda N.: Genetic and antigenic diversity among noroviruses. J. Gen. Virol. 87: 909-919, 2006. 19) Marionneau S, Ruvoen N, Le Moullac-Vaidye B, Clement M, Cailleau-Thomas A, Ruiz-Palacois G, Huang P, Jiang X, Le Pendu J.: Norwalk virus binds to histo-blood group antigens present on gastroduodenal epithelial cells of secretor individuals. Gastroenterology. 122:1967-1977, 2002. 4) Graham DY, Jiang X, Tanaka T, Opekun AR, Madore HP, Estes MK.: Norwalk virus infection of volunteers: new insights based on improved assays. J. Infect. Dis. 170: 34-43, 1994. 8) Huang P, Farkas T, Marionneau S, Zhong W, Ruvoën-Clouet N, Morrow AL, Altaye M, Pickering LK, Newburg DS, LePendu J, Jiang X.: Noroviruses bind to human ABO, Lewis, and secretor histo-blood group antigens: identification of 4 distinct strain-specific patterns. J. Infect. Dis. 188, 19-31. (2003 9) Huang P, Farkas T, Zhong W, Tan M, Thornton S, Morrow AL, Jiang X.: Norovirus and histo-blood group antigens: demonstration of a wide spectrum of strain specificities and classification of two major binding groups among multiple binding patterns. J. Virol. 79, 6714-6722, 2005. 2) Chakravarty, S., Hutson, A. M., Estes, M. K., Prasad, B. V. V.: Evolutionary Trace Residues in Noroviruses: Importance in Receptor Binding, Antigenicity, Virion Assembly, and Strain Diversity. J. Virol. 79: 554-568, 2005. 13) Jiang X, Graham DY, Wang K, Estes MK.: Norwalk virus genome cloning and characterization. Science 250: 1580-1583, 1990. 24) Rockx BH, Vennema H, Hoebe CJ, Duizer E, Koopmans MP.: Association of histo-blood group antigens and susceptibility to norovirus infections. J. Infect. Dis. 191: 749-754, 2005. 18) Lindesmith L, Moe C, Marionneau S, Ruvoen N, Jiang X, Lindblad L, Stewart P, LePendu J, Baric R.: Human susceptibility and resistance to Norwalk virus infection. Nat. Med. 9: 548-553, 2003. 27) Tan M, Huang P, Meller J, Zhong W, Farkas T, Jiang X.: Mutations within the P2 domain of norovirus capsid affect binding to human histo-blood group antigens: evidence for a binding pocket. J. Virol. 77: 12562-12571, 2003. 22) Okada M, Tanaka T, Oseto M, Takeda N, Shinozaki K.: Genetic analysis of noroviruses associated with fatalities in healthcare facilities. Arch. Virol. 151: 1635-1641, 2006. 14) Jiang X, Wang M, Wang K, Estes MK.: Sequence and genomic organization of Norwalk virus. Virology 195: 51-61, 1993. 6) Harrington PR, Lindesmith L, Yount B, Moe CL, Baric RS.: Binding of Norwalk virus-like particles to ABH histo-blood group antigens is blocked by antisera from infected human volunteers or experimentally vaccinated mice. J. Virol. 76: 12335-12343, 2002. 12) Hutson AM, Atmar RL, Marcus DM, Estes MK.: Norwalk virus-like particle hemagglutination by binding to h histo-blood group antigens. J Virol 77: 405-415, 2003. 25) Ruvoen-Clouet N, Ganiere JP, Andre-Fontaine G, Blanchard D, Le Pendu J.: Binding of rabbit hemorrhagic disease virus to antigens of the ABH histo-blood group family. J. Virol. 74: 11950-11954, 2000. 26) Shirato-Horikoshi H, Ogawa S, Wakita T, Takeda N, Hansman GS.: Binding activity of norovirus and sapovirus to histo-blood group antigens. Arch. Virol. 152: 457-461, 2007. |
References_xml | – reference: 10) Hutson AM, Atmar RL, Estes MK.: Norovirus disease: changing epidemiology and host susceptibility factors. Trends Microbiol 12: 279-287, 2004. – reference: 16) Kaneko M, Nishihara S, Shinya N, Kudo T, Iwasaki H, Seno T, Okubo Y, Narimatsu H.: Free Full Text Wide variety of point mutations in the H gene of Bombay and para-Bombay individuals that inactivate H enzyme. Blood 90: 839-849, 1997. – reference: 20) Narimatsu H, Iwasaki H, Nakayama F, Ikehara Y, Kudo T, Nishihara S, Sugano K, Okura H, Fujita S, Hirohashi S.: Lewis and secretor gene dosages affect CA19-9 and DU-PAN-2 serum levels in normal individuals and colorectal cancer patients. Cancer Res. 58: 512-518, 1998. – reference: 7) Harrington, P. R., Vinjé J, Moe CL, Baric RS.: Norovirus capture with histo-blood group antigens reveals novel virus-ligand interactions. J. Virol. 78: 3035-3045, 2004. – reference: 13) Jiang X, Graham DY, Wang K, Estes MK.: Norwalk virus genome cloning and characterization. Science 250: 1580-1583, 1990. – reference: 21) Okada M, Ogawa T, Kaiho I, Shinozaki K.: Genetic analysis of noroviruses in Chiba Prefecture, Japan, between 1999 and 2004. J. Clin. Microbiol. 43: 4391-4401, 2005. – reference: 12) Hutson AM, Atmar RL, Marcus DM, Estes MK.: Norwalk virus-like particle hemagglutination by binding to h histo-blood group antigens. J Virol 77: 405-415, 2003. – reference: 6) Harrington PR, Lindesmith L, Yount B, Moe CL, Baric RS.: Binding of Norwalk virus-like particles to ABH histo-blood group antigens is blocked by antisera from infected human volunteers or experimentally vaccinated mice. J. Virol. 76: 12335-12343, 2002. – reference: 18) Lindesmith L, Moe C, Marionneau S, Ruvoen N, Jiang X, Lindblad L, Stewart P, LePendu J, Baric R.: Human susceptibility and resistance to Norwalk virus infection. Nat. Med. 9: 548-553, 2003. – reference: 19) Marionneau S, Ruvoen N, Le Moullac-Vaidye B, Clement M, Cailleau-Thomas A, Ruiz-Palacois G, Huang P, Jiang X, Le Pendu J.: Norwalk virus binds to histo-blood group antigens present on gastroduodenal epithelial cells of secretor individuals. Gastroenterology. 122:1967-1977, 2002. – reference: 15) Kageyama T, Shinohara M, Uchida K, Fukushi S, Hoshino FB, Kojima S, Takai R, Oka T, Takeda N, Katayama K. (2004) Coexistence of multiple genotypes, including newly identified genotypes, in outbreaks of gastroenteritis due to Norovirus in Japan. J. Clin. Microbiol. 42, 2988-2995 – reference: 26) Shirato-Horikoshi H, Ogawa S, Wakita T, Takeda N, Hansman GS.: Binding activity of norovirus and sapovirus to histo-blood group antigens. Arch. Virol. 152: 457-461, 2007. – reference: 5) Hansman GS, Natori K, Shirato-Horikoshi H, Ogawa S, Oka T, Katayama K, Tanaka T, Miyoshi T, Sakae K, Kobayashi S, Shinohara M, Uchida K, Sakurai N, Shinozaki K, Okada M, Seto Y, Kamata K, Nagata N, Tanaka K, Miyamura T, Takeda N.: Genetic and antigenic diversity among noroviruses. J. Gen. Virol. 87: 909-919, 2006. – reference: 22) Okada M, Tanaka T, Oseto M, Takeda N, Shinozaki K.: Genetic analysis of noroviruses associated with fatalities in healthcare facilities. Arch. Virol. 151: 1635-1641, 2006. – reference: 14) Jiang X, Wang M, Wang K, Estes MK.: Sequence and genomic organization of Norwalk virus. Virology 195: 51-61, 1993. – reference: 17) Kudo T, Iwasaki H, Nishihara S, Shinya N, Ando T, Narimatsu I, Narimatsu H.: Molecular genetic analysis of the human Lewis histo-blood group system. II. Secretor gene inactivation by a novel single missense mutation A385T in Japanese nonsecretor individuals. J Biol Chem 271: 9830-9837, 1996. – reference: 9) Huang P, Farkas T, Zhong W, Tan M, Thornton S, Morrow AL, Jiang X.: Norovirus and histo-blood group antigens: demonstration of a wide spectrum of strain specificities and classification of two major binding groups among multiple binding patterns. J. Virol. 79, 6714-6722, 2005. – reference: 1) Cao, S., Lou, Z., Tan, M., Chen, Y., Liu, Y., Zhang, Z., Zhang, X. C., Jiang, X., Li, X., Rao, Z.: Structural Basis for the Recognition of Blood Group Trisaccharides by Norovirus. J. Virol. 81: 5949-5957, 2007. – reference: 3) Glass PJ, White LJ, Ball JM, Leparc-Goffart I, Hardy ME, Estes MK.: Norwalk virus open reading frame 3 encodes a minor structural protein. J. Virol. 74: 6581-6591, 2000. – reference: 11) Hutson AM, Atmar RL, Graham DY, Estes MK.: Norwalk virus infection and disease is associated with ABO histo-blood group type. J. Infect. Dis. 185: 1335-1337, 2002. – reference: 8) Huang P, Farkas T, Marionneau S, Zhong W, Ruvoën-Clouet N, Morrow AL, Altaye M, Pickering LK, Newburg DS, LePendu J, Jiang X.: Noroviruses bind to human ABO, Lewis, and secretor histo-blood group antigens: identification of 4 distinct strain-specific patterns. J. Infect. Dis. 188, 19-31. (2003) – reference: 23) Prasad, B. V. V., Hardy ME, Dokland T, Bella J, Rossmann MG, Estes MK.: X-ray crystallographic structure of the Norwalk virus capsid. Science 286: 287-290, 1999. – reference: 25) Ruvoen-Clouet N, Ganiere JP, Andre-Fontaine G, Blanchard D, Le Pendu J.: Binding of rabbit hemorrhagic disease virus to antigens of the ABH histo-blood group family. J. Virol. 74: 11950-11954, 2000. – reference: 2) Chakravarty, S., Hutson, A. M., Estes, M. K., Prasad, B. V. V.: Evolutionary Trace Residues in Noroviruses: Importance in Receptor Binding, Antigenicity, Virion Assembly, and Strain Diversity. J. Virol. 79: 554-568, 2005. – reference: 4) Graham DY, Jiang X, Tanaka T, Opekun AR, Madore HP, Estes MK.: Norwalk virus infection of volunteers: new insights based on improved assays. J. Infect. Dis. 170: 34-43, 1994. – reference: 27) Tan M, Huang P, Meller J, Zhong W, Farkas T, Jiang X.: Mutations within the P2 domain of norovirus capsid affect binding to human histo-blood group antigens: evidence for a binding pocket. J. Virol. 77: 12562-12571, 2003. – reference: 24) Rockx BH, Vennema H, Hoebe CJ, Duizer E, Koopmans MP.: Association of histo-blood group antigens and susceptibility to norovirus infections. J. Infect. Dis. 191: 749-754, 2005. |
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Title | ノロウイルスと血液型抗原 |
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