Molecular epidemiology of HIV and the genetic factors influencing AIDS disease progression in Asia

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 16256002
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 海外学術
• Research Field: Virology
• Research Institution: NATIONAL INSTITUTE OF INFECTIOUS DISEASES
• Principal Investigator: TAKEBE Yutaka NIID, AIDS RESEARCH CENTER, CHIEF, エイズ研究センター, 室長 (50126116)
• Co-Investigator(Kenkyū-buntansha): KUSAGAWA Shigeru NIID, AIDS RESEARCH CENTER, SENIOR RESEARCHER, エイズ研究センター, 主任研究者 (10267990) ; SHIINO Teiichiro NIID, AIDS RESEARCH CENTER, SENIOR RESEARCHER, エイズ研究センター, 主任研究者 (90291129) ; SHIODA Tatsuo OSAKA UNIV., PROFESSOR, 医学部微生物病研究所・免疫・生体防御研究部, 教授 (00187329) ; OKA Shinichi INTERNATIONAL MEDICAL CENTER OF JAPAN, DIRECTOR, エイズ治療・研究開発センター, 部長 (20194326)
• Project Period (FY): 2004 – 2006
• Keywords: ASIA / HIV / MOLECULAR EPIDEMIOLOGY / SUBTYPE / CRF / RECOMBINATION / DISEASE / GENETIC FACTORS

Research Abstract

(1)Molecular epidemiology of HIV in Asia :
We investigated the molecular epidemiology of HIV in several study sites in Asia to elucidate the interrelationships of the epidemics with those of surrounding regions and of different risk populations. In China, we found the close Interrelationships of the epidemics between IDU/former plasma donor (FPD) and heterosexuals. In particular, HIV-1 subtype B, the strain responsible for the tragic outbreaks In central China, is found to predominate among heterosexuals. This urges the urgent need for implementation of effective measures to prevention the Infections into general population in China.
HIV-1 nomenclature system is becoming very complicated as the time goes by. A major HIV-1 strain, HIV-1 group M, responsible for the current pandemic is classified at least 11 subtypes and subsubtypes and 34 circulating recombinant forms (CRFs) so far. We identified the 33rd CRF (CRF33_01B) among IDU and heterosexuals in Malaysia. This is the first CRF reported from a research group in Japan that was officially approved by international HIV sequence databases.
(2)Investigation of virus and host factors influencing the disease progression to AIDS :
The rate of disease progression to AIDS is influenced greatly by several factors : most Importantly viral and host factors. We for the first time identified the case of CRF01_AE infection with gross deletions in nef-LTR regions among a long-term nonprogressor in Asia. This is the first case of nef-LTR deletion found among nonsubtype B strains, associated with slower disease progression. For the host factors, Dr.Shioda and his colleagues confirmed the significant protective effect of IL4-589T and RANTES-28G on HV disease progression in their study conducted in Thailand.
These findings could provide the information critical for understanding the genesis of HIV/AIDS epidemic in Asia and for the future vaccine strategies to prevent HIV spread in Asia.

Research Products

• [Journal Article] Molecular epidemiology of HIV (Update) : Understanding the genesis of global AIDS epidemic. (2007)
  • Author(s): Takebe, Y., Uenishi, R., Li, S.
  • Journal Title: Book Chapter for "HIV : Molecular biology and pathogenesis : viral mechanisms : 48" (Elsevier Book series) (in press)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Identification of a novel circulating recombinant form (CRF33_01B) disseminating widely among various risk populations in Kuala Lumpur, Malaysia. (2006)
  • Author(s): Tee, K.K., Li, X.-J., Nohtomi, K., Ng, K.P., Kamarulzaman, A., Takebe, Y.
  • Journal Title: J. AIDS 43(5) Pages: 523-529
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Protective effects of IL4-589T and RANTES-28G on HIV-1 disease progression in infected Thai females. (2006)
  • Author(s): Wichukchinda, N., Nakayama, E, E., Rojanawiwat, A, Pathipvanich, P., Auwanit, S-V., Ariyoshi, K., Sawanpanyalert, P., Shioda, T.
  • Journal Title: AIDS 20 Pages: 189-196
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] siVirus : web-based antiviral siRNA design software for highly divergent viral sequences. (2006)
  • Author(s): Naito, Y., Ui-Tei, K., Nishikawa, T., Takebe, Y., Saigo, K.
  • Journal Title: Nucl. Acid Res. 34 Pages: W448-W450
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Evidence for the acquisition of multidrug resistance by an HIV clinical isolate via human sequence transduction. (2006)
  • Author(s): Takebe, Y., Telesnitsky, A.
  • Journal Title: Virology 351 Pages: 1-6
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification of a novel circulating recombinant form (CRF33_01B) disseminating widely among various risk populations in Kuala Lumpur, Malaysia. (2006)
  • Author(s): Tee, K.K., Li, X.-J., Nohtomi, K., Ng, K.P., Kamarulzaman, A., Takebe, Y.
  • Journal Title: J.AIDS 43(5) Pages: 523-529
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Protective effects of IL4-589T and RANTES-28G on HIV-1 disease progression in infected Thai females. (2006)
  • Author(s): Wichukchinda, N., Nakayama, E, E., Rojanawiwat, A., Pathipvanich, P., Auwanit, S-V., Ariyoshi, K., Sawanpanyalert, P., Shioda, T.
  • Journal Title: AIDS 20 Pages: 189-196
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Modified dynabeads method for enumerating CD4+ T-lymphocyte count for widespread use in resource-limited situations. (2006)
  • Author(s): Bi, X., Gatanaga, H., Tanaka, M., Hnda, M., Ida, S., Kimura, S., Oka, S.
  • Journal Title: Acquir Immune Dific Syndr. 38 Pages: W448-W450
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] web-based antiviral siRNA design software for highly divergent viral sequences. (2006)
  • Author(s): Naito, Y., Ui-Tei, K., Nishikawa, T., Takebe, Y., Saigo, K.siVirus
  • Journal Title: Nucl.Acid Res 34 Pages: 1-6
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Molecular Epidemiology of the Heterosexual HIV-1 Epidemic in Kunming, Yunnan Province, China, Suggests Origin from the Local IDU Epidemic. (2005)
  • Author(s): Li, X.-J., Kusagawa, S., Xia, X., Yang, C., Wang, Q., Yokota, Y., Hoshina, Y., Onogi, T., Nohtomi, K., Imamura, Y., Shiino, T., Yang, R., Yamamoto, N., Ben, K., Takebe, Y.
  • Journal Title: AIDS Res and Human Retroviruses 21 Pages: 977-980
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification of attenuated HIV-1 CRF01_AE variant associated with slow disease progression due to gross genetic alterations in the nef-LTR sequences. (2005)
  • Author(s): Kondo, M., Shima, T., Sudo, K., Nishizawa, M., Iwamuro, S., Okabe, T., Takebe, Y., Imai, M.
  • Journal Title: J. Inf Dis 192 Pages: 56-61
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Modified dynabeads method for enumerating CD4+ T-lymphocyte count for widespread use in resource-limited situations. (2005)
  • Author(s): Bi, X., Gatanaga, H., Tanaka, M., Hnda, M., Ida, S., Kimura, S., Oka, S.
  • Journal Title: Acquir Immune Dific Syndr. 38 Pages: 1-4
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Identification of attenuated HIV-1 CRFOI_AE variant associated with slow disease progression due to gross genetic alterations in the nef-LTR sequences. (2005)
  • Author(s): Kondo, M., Shima, T., Sudo, K., Nishizawa, M., Iwamuro, S., Okabe, T., Takebe, Y., Imai, M.
  • Journal Title: J.Inf Dis 192 Pages: 56-81
  • Description: 「研究成果報告書概要(欧文)」より
• [Book] Book Chapter for "HIV : Molecular biology and pathogenesis : viral mechanisms : 48" (Elsevier Book series) (2007)
  • Author(s): Takebe, Y., Uenishi, R., Li, S.
  • Publisher: Molecular epidemiology of HIV (Update) : Understanding the genesis of global AIDS epidemic.(in press)
  • Description: 「研究成果報告書概要(和文)」より