Molecular and viral research on dengue hemorrhagic fever

• Project/Area Number: 15406020
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 海外学術
• Research Field: Virology
• Research Institution: Nagasaki University
• Principal Investigator: MORITA Kouichi Nagasaki University, Institute of Tropical Medicine, Professor (40182240)
• Co-Investigator(Kenkyū-buntansha): INOUE Shingo Nagasaki University, Institute of Tropical Medicine, Research Associate (00346925) ; KUMATORI Atsushi Nagasaki University, Institute of Tropical Medicine, Assistant Professor (60244092) ; TADANO Masayuki Ryukyu University, School of Medicine, Associate Professor (80179712) ; TSUDA Yoshio Nagasaki University, National Institute of Infectious Disease, Chief (20207393) ; マンモハン パリダ 長崎大学, 熱帯医学研究所, 助手 (60380953) ; 長谷部 太 長崎大学, 熱帯医学研究所, 講師 (20253693)
• Project Period (FY): 2003 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥10,000,000 (Direct Cost: ¥10,000,000); Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000); Fiscal Year 2004: ¥4,200,000 (Direct Cost: ¥4,200,000); Fiscal Year 2003: ¥3,600,000 (Direct Cost: ¥3,600,000)
• Keywords: dengue hemorrhagic fever / molecular epidemiology / mosquito borne tropical disease / dengue virus / flow cytometry analysis / デング熱・デング出血熱 / ウイルス性出血熱 / 熱帯病 / 蚊媒介性疾患 / 血小板減少

Research Abstract

In order to elucidate various virus and host factors that are relevant to the development of dengue hemorrhagic fever, we conducted a three-year research project. We isolated a number of dengue virus strains during dengue epidemic in Bangladesh, the Philippines, and Vietnam and determined nucleotide sequences of the virus strains. The data was compared with each other as well as the sequences obtained in conventional data base. We witnessed the genotype shift of dengue virus 2 in the Philippines during the early 2000s from local strain to cosmopolitan strain. While in Bangladesh and Vietnam, dengue viruses evolved locally and caused periodic epidemics in the countries. In the comparisons made with viruses from dengue hemorrhagic fever and dengue fever, we could not detect any significant differences between the two groups. In the flow cytometry analysis, we clearly demonstrated that dengue virus can infect peripheral B cells and NK cells suggesting the target of dengue virus in humans is not always on a particular cell group but the virus can choose the target cells according to its affinity to each virus group.
This idea was further strengthened later by the fact that two distinct virus strains were isolated from one patient by using different cell lines for isolation. One virus stain was isolated by mosquito cells and grow well in the cells but not human B cell line. While the other virus was isolated by K562, a culture cell line form human monocyte, grow well in B cell lines. Those two viruses possessed an amino acid alternation in E protein, suggesting a determinant of cell tropism. It is very likely that dengue virus population gap may have some effect to determine dengue virus pathogenesis in human infection. Further clarification of the importance of this dengue virus population gap is necessary to understand the mechanism to determine the severity in dengue virus infections in humans.

Research Products

• [Journal Article] Phylogenetic analysis of dengue viruses isolated from imported dengue patients:possible aid for determining the countries where infections occurred (2007)
  • Author(s): Ito M, Y amada K, Takasaki T, Pandey B Nerome R, Tajima S, Morita K, Kurane I.
  • Journal Title: J Travel Med. 14 Pages: 233-244
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Phylogenetic analysis of dengue viruses isolated from imported dengue patients : possible aid for determining the countries where infections occurred. (2007)
  • Author(s): ItoM, Yamada K, Takasaki T, Pandey B, Nerome R, Tajima S, Morita K, Kurane I.
  • Journal Title: J Travel Med. Vol.14(4) Pages: 233-44
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Molecular Characterization and Clinical Evaluation of Dengue Outbreak in 2002 in Bangladesh (2006)
  • Author(s): Islam M.A., Ahmed M.U., Begum N., C howdhury N.A., Khan A.F., Parquet M.C, Bipolo S., Inoue S., Hasebe F., Suzuki Y., Morita K.
  • Journal Title: Japanese Journal of Infectious Diseases 59 Pages: 85-91
  • NAID: 120006983661
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Molecular Characterization and Clinical Evaluation of Dengue Outbreak in 2002 in Bangladesh. (2006)
  • Author(s): Islam MA., Ahmed MU., Begum N., Chowdhury NA., Khan AF. Parquet MC, Bipolo S., Inoue S., Hasebe F., Suzulci Y., Morita K.
  • Journal Title: Japanese Journal of Infectious Diseases Vol.59 Pages: 85-91
  • NAID: 120006983661
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification and Characterization of Carbohydrate Molecules in Mammalian Cells Recognized by Dengue Virus Type 2. (2006)
  • Author(s): Aoki, C., HidariK.IPJ., Itonori, S., Yarnada, A., Takahashi, N.Kasama, T., Hasebe, F., Islam, MA., Hatano, K., Matsuoka, K., Taki, T., Guo, C-T., Takahashi, T., Sakano, Y., Suzuki, T., Miyamoto, D., Sugita, M., Terunuma, D., Morita, K., Suzuki, Y.
  • Journal Title: Journal of Biochemistry Vol.139 Pages: 6007-614
  • NAID: 10018847231
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Molecular Epidemiology of dengue 2 viruses in the Philippines (2005)
  • Author(s): L.Salda, M.Parquet, R.Matias, F.Nati vidad, n.Kobayashi, K.Morita
  • Journal Title: American Journal Tropical Medicine and Hygiene 73 Pages: 796-802
  • Description: 「研究成果報告書概要(和文)」より
  • Peer Reviewed
• [Journal Article] Natividad, Nobuyuki Kobayashi, Kouichi Morita. Molecular Epidemiology of dengue 2 viruses in the Philippines : Genotype shift and local evolution. (2005)
  • Author(s): Leonora TD Salda, Maria DCParquet, Ronald R. Matias, Filipinas F.
  • Journal Title: Am.J.Trop.Med.Hyg. Vol.73 Pages: 796-802
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Immunoglobulin A Antibody Responses in Dengue Patients : a Useful Marker for Sero diagnosis of Dengue Virus Infection. (2005)
  • Author(s): Nawa M., Takasaki T., Ito M., Inoue S., Morita K., Kurane I.
  • Journal Title: Clinical and Diagnostic Laboratory Immunology. Vol.12 Pages: 1235-1237
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Molecular Epidemiology of dengue 2 viruses in the Philippines Genotype shift and local evolution. (2005)
  • Author(s): Leonora T.D.Salda, 他5名
  • Journal Title: Am.J.Trop.Med.Hyg 73 Pages: 796-802
• [Journal Article] Immunoglobulin A Antibody Responses in Dengue Patients : a Useful Marker for Sero diagnosis of Dengue Virus Infection (2005)
  • Author(s): Nawa M.他5名
  • Journal Title: Clinical and Diagnostic Laboratory Immunology. 12 Pages: 1235-1237
• [Journal Article] Comparison of Clinical Features and Hematologic Abnormalities Between Dengue Fever and Dengue Hemorrhagic Fever Among Children in the Philippines. (2005)
  • Author(s): Celia C.Carlos, 他15名
  • Journal Title: Am.J.Trop.Med.Hyg. 73 Pages: 435-440
• [Journal Article] Rapid Detection and Differentiation of Dengue Virus Serotypes by a Real-Time Reverse Transcription-Loop -Mediated Isothermal Amplification Assay. (2005)
  • Author(s): Manmohan Parida, 他9名
  • Journal Title: J.Clin.Microbiol. 43 Pages: 2895-2903
• [Journal Article] Molecular basis for adaptation of a chimeric dengue type4/Japanese encephalitis virus to vero cells (2005)
  • Author(s): Wei-Feng Tang, 他4名
  • Journal Title: Microbiol.Immunol 49 Pages: 285-294
• [Journal Article] フラビウイルスによる疾患(ウエストナイル熱、デング熱を中心に (2005)
  • Author(s): 森田公一
  • Journal Title: カレントテラピー 27 Pages: 722-724
• [Journal Article] Fusion PCR generated Japanese encephalitis virus/dengue 4 virus chimera exhibits lack of neuroinvasiveness, attenuated neurovirulence, and a dual-flavi immune response in mice. (2004)
  • Author(s): Mathenge, EMG, K.Morita 他7名
  • Journal Title: Journal of General Virology. 85 Pages: 2503-2513
• [Journal Article] Shift in JEV genotype circulating in northern Vietnam : Implication for frequent introductions of JEV from Southeast Asia to East Asia (2004)
  • Author(s): Nga PT, K.Morita 他8名
  • Journal Title: Journal of General Virology. 85 Pages: 1625-1631
• [Journal Article] Real-time reverse transcription loop mediated isothermal amplification for rapid detection of West Nile virus (2004)
  • Author(s): Parida M., Morita K.他3名
  • Journal Title: J.Clin.Microbiol. 42 Pages: 257-263
• [Presentation] Studies on anti-dengue compounds that inhibit cell entry (2006)
  • Author(s): Morita K.
  • Organizer: International Dengue Symposium
  • Place of Presentation: India,Pune
  • Year and Date: 2006-11-10
  • Description: 「研究成果報告書概要(和文)」より
• [Presentation] Studies on anti-dengue compounds that inhibit cell entry. (2006)
  • Author(s): Morita K.
  • Organizer: International Symposium on Dengue
  • Place of Presentation: Pune, India
  • Year and Date: 2006-11-10
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Identification and characterization of carbohydrate determinant that is recognized with domain III of dengue virus envelope glycoprotein. (2006)
  • Author(s): Hidari K., Aoki C., Yamada A., Hasebe F., Islam MA., Hatano K., Matsuoka K., Guo CT., Takahashi T., Sakano Y., Suzuki T., Miyamoto D., Terumura D., Morita K., Suzuki Y.
  • Organizer: 20th IUBMB International Congress of Biochemistry and Molecular Biology and 11th FAOBMB Congress.
  • Place of Presentation: Kyoto, Japan
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Real-Time Reverse Transcription Loop Mediated Isothermal Amplification(RT-LAMP) Assay as a rapid diagnostic tool for Emerging Viruses. (2004)
  • Author(s): Panda M., Minekawa H., Notomi T., Inoue S., Hasebe F., Morita K.
  • Organizer: 53rd Annual Meeting of American Society of Tropical Medicine and Hygiene.
  • Place of Presentation: Miami, Florida, USA
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] TNF-α promoter polymorphism and DHF in Vietnam. (2004)
  • Author(s): Hirayama K., Kikuchi M., Huong V. T. Q., Ngu V. T. T., Tham V. D., Dat T. V., Ha D. Q., Morita K.
  • Organizer: Nagasaki Symposium on Tropical Emerging Infectious Diseases and JSPS Workshop on Infectious Diseases in Vietnam.
  • Place of Presentation: Nagasaki, Japan
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Association of increased platelet-associated immunoglobulins with thrombocytopenia and the severity of disease in secondary dengue virus infections. (2004)
  • Author(s): Oishi K., Saito M., Inoue S., Dimaano E. M., Alera M. T. P., Robles M. P., Estrella, Jr. B. D., Kumatori A., Moji K., Alonzo B. M., Buerano C. C., Matias R. R., Morita K., Natividad F. F., Nagatake T.
  • Organizer: Nagasaki Symposium on Tropical Emerging Infectious Diseases and JSPS Workshop on Infectious Diseases in Vietnam.
  • Place of Presentation: Nagasaki, Japan
  • Description: 「研究成果報告書概要(欧文)」より
• [Presentation] Molecular Epidemiology of Dengue 4 Virus in Vietnam ; Identification of New Genotypes and Evidence of Local Independent Evolution. (2004)
  • Author(s): Parquet M. D. C., Huong V. T. Q., Mai L. T. Q., Hasebe F., Inoue S., Morita K.
  • Organizer: Fortieth U. S.-Japan Cooperative Medical Science Program.
  • Place of Presentation: Kyoto, Japan
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] 今日の治療指針(デング熱, デシグ出血熱) (2005)
  • Author(s): 森田 公一
  • Publisher: 医学書院
  • Description: 「研究成果報告書概要(和文)」より
• [Book] 今日の治療指針 「デング熱、デング出血熱」
  • Author(s): 森田公一 (分担執筆)
  • Publisher: 医学書院
• [Publications] Inoue S., Morita et al.: "and Natividad F.F.Distribution of three arbovirus antibodies among monkeys (Macaca facscicularis) in the Philippines"J.Med.Primatol.. 32. 89-94 (2003)
• [Publications] Ohishi K., Inoue S.et al.: "Correlation between increased platelet-associated IgG and thronbocytopecia in secondary dengeu virus infections"J.Med.Virol.. 71. 259-264 (2003)
• [Publications] Oishi K., Inoue A.et al.: "Association of dengue virus type-specific IGG on platelets is specific for the acute phase in an imported dengue patient with seconday dengue virus infection"J.J.Trop.Med.Hygn.. 31. 223-225 (2003)
• [Publications] 森田公一: "デング熱・デング出血熱(新世紀の感染症学上)"日本臨床. 61. 302-305 (2003)