Analysis of mechanism of HIV mucosa' infection and immunity using SHIV-monkey system

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 14021046
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Kyoto University
• Principal Investigator: HAYAME Masanori Kyoto University, Institute for Virus Research, Professor, ウイルス研究所, 教授 (40072946)
• Co-Investigator(Kenkyū-buntansha): IDO Eiji Kyoto University, Institute for Vitus Research, Assistant professor, ウイルス研究所, 助手 (70183176)
• Project Period (FY): 2002 – 2005
• Keywords: AIDS / DNA vaccine / AIDS vaccine / SIV / SHIV / monkev / mucosal infection / mucosal immunity

Research Abstract

In order to clarify the mechanisms of mucosal infection and mucosal immunity of HIV-1, we have tried to establish the monkey experimental model system of mucosal infection using SIV and SHIV and to see the virus spread and immune response for protection. Results obtained are followed.
1. Immunities and protective effect of nonpathogenic SHIV against mucosal infection (2001).
Involvement of 7 5 T and NK as well as acquired immunities was shown in the protection against intrarectal attack infection of pathogenic SHIV in the monkeys immunized with nef-deleted nonpathogenic SHIV.
2. Virus population through SIV intravaginal infection (2002).
Virus population was restricted when it passed through mucosa and it had no relation to viral cell tropisms.
3. Virus spread and immune responses at the early phase of intrarectal infection of acute pathogenic SHIV (2003).
Immediately after intrarectal infection, the virus spread in a whole body, not replicating at the mucosal sites. The CD4 cell decrease was prominent especially in thymus in which impairment of T cell maturation was ex vivo demonstrated.
4. Virus spread and immune responses at the early phase of intrarectal infection of low pathogenic SHIV (2004).
Virus replicated and induced CD4 cell depletion at the rectal sites, and gradually spread to a whole body in which CD4 depletion was slight.
5. Vaccination with SHIV DNA which produces noninfectious virions protected mucosal infection (2005).
SHIV mutant DNA lacking packaging ability induced protective effect against intrarectal attack infection of acute pathogenic SHIV.
Close association of virus spread and immure response with prognosis had been suggested in HIV1 infection. This study experimentally proved it by using monkeys. The obtains results are important and useful for develonment of effeetive vaepine develonment

Research Products

• [Journal Article] DNA vaccination of macaques by a full-genome SHIV plasmid that has an IL-2 gene and produces non-infection virus particles (2006)
  • Author(s): Horiuchi, R., Akahata, W., Kuwata, T., Enose, Y., Ido, E., Suzuki, H., Miyake, A., Saito, N., Ibuki, K., Goto, T., Miura, T., Hayami, M.
  • Journal Title: Vaccine 24,17 Pages: 3677-3685
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] DNA vaccination of macaques by a full-genome SHIV plasmid that has an IL-2 gene and produces non-infectious virus particles (2006)
  • Author(s): Horiuchi, R., Akahata, W., Kuwata, T., Enose, Y., Ido, E., Suzuki, H., Miyake, A., Saito, N, Ibuki, K., Goto, T., Miura, T., Hayami, M.
  • Journal Title: Vaccine 24(17) Pages: 3677-3685
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The quantity and diversity of infection viruses in various tissues of SHIV-infected monkeys at the early and AIDS stages (2004)
  • Author(s): Miyake, A., Enose, Y., Ohkura, S., Suzuki, H., Kuwata, T., Shimada, T., Kato, S., Narayan, O., Hayami, M.
  • Journal Title: Arch. Virol. 149 Pages: 943-955
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The quantity and diversity of infectious viruses in various tissues of SHIV-infected monkeys at the early and AIDS stages (2004)
  • Author(s): Miyake, A., Enose, Y., Ohkura, S., Suzuki, H., Kuwata, T., Shimada, T., Kato, S., Narayan, O., Hayami,M.
  • Journal Title: Arch. Virol. 149 Pages: 943-955
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] DNA vaccination of macaques by a full genome SHIV-1 plasmid chimera that produces non-infectious virus particles (2003)
  • Author(s): Akahata, W., Ido, E., Akiyama, H., Uesaka, H., Enose, Y., Horiuchi, R., Kuwata, T., Goto, T., Takahashi, H., Hayami, M.
  • Journal Title: J. Gen. Virol. 84 Pages: 2237-2244
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Construction and in vivo infection of anew simian/human immunodeficiency virus chimera containing the reverse transcriptasegene and the 3' half of the genomic region of human immunodeficiency virus type 1 (2003)
  • Author(s): Akiyama, H., Ido, E., Akahata, W., Kuwata, T., Miura, T., Hayami, M.
  • Journal Title: J. Gen. Virol. 84 Pages: 1663-1669
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Construction and in vivo infection of a new simian/human immunodeficiency virus chimera containing the reverse transcriptase gene and the 3' half of the genomic region of human immunodeficiency virus type 1 (2003)
  • Author(s): Akiyama, H., Ido, E., Akahata, W, Kuwata, T., Miura, T., Hayami, M.
  • Journal Title: J. Gen. Virol. 84 Pages: 1663-1669
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Protection by intranasal immunization of anef-deleted, nonpathogenic SHIV against intravaginal challenge with a heterologous pathogenic SHIV (2002)
  • Author(s): Enose, Y., Ui, M., Miyake, A., Suzuki, H., Uesaka, H., Kuwata, T., Kunisawa, J., Kiyono, H., Takahashi, H., Miura, T., Hayami, M.
  • Journal Title: Virology. 298 Pages: 306-316
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Protection by intranasal immunization of a nef-deleted, nonpathogenic SHIV against intravaginal challenge with a heterologous pathogenic SHIV (2002)
  • Author(s): Enose, Y., Ui, M., Miyake, A., Suzuki, H., Uesaka, H., Kuwata, T., Kunisawa, J., Kiyono, H., Takahashi, H., Miura, T., Hayami,M.
  • Journal Title: Virology. 298 Pages: 306-316
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Characterrization of less pathogenic infectious molecular clones derived from acute-pathogrnic ShIV-89.6P stock virus (2001)
  • Author(s): Kozyrev, IL., Ibuki, K., Shimada, T., Kuwata, T., Takemura, T., Hayami, M., Miura, T.
  • Journal Title: Virology. 282 Pages: 6-13
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Characterization of less pathogenic infectious molecular clones derived from acute-pathogenic SHIV-89.6P stock virus (2001)
  • Author(s): Kozyrev, 1 L., Ibuki, K., Shimada, T., Kuwata, T., Takemura, T., Hayami, M., Miura, T.
  • Journal Title: Virology 282 Pages: 6-13
  • Description: 「研究成果報告書概要(欧文)」より