Host genetic polymorphisms that can affect HIV diseases.

• Project/Area Number: 14021056
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: SHIODA Tatsuo Osaka University, Research Institute for Microbial Diseases, Professor, 微生物病研究所, 教授 (00187329)
• Project Period (FY): 2002 – 2005
• Project Status: Completed (Fiscal Year 2005)
• Budget Amount: ¥56,000,000 (Direct Cost: ¥56,000,000); Fiscal Year 2005: ¥15,000,000 (Direct Cost: ¥15,000,000); Fiscal Year 2004: ¥15,000,000 (Direct Cost: ¥15,000,000); Fiscal Year 2003: ¥16,000,000 (Direct Cost: ¥16,000,000); Fiscal Year 2002: ¥10,000,000 (Direct Cost: ¥10,000,000)
• Keywords: HIV-1 / chemokine / chemokine receptor / cytokine, genetic / polymorphism / disease progression / サイトカン

Research Abstract

1. CCR5 is an essential coreceptor for the cellular entry of R5 strains of human immunodeficiency virus type 1 (HIV-1). CCR5-893(-) is a single-nucleotide deletion mutation which is observed exclusively in Asians. We found that the CCR5-893(-) mutation affects intracellular transport of CCR5 and raise the possibility that this mutation also affects HIV-1 transmission and disease progression.
2. A valine to isoleucine substitution at position 64 of CCR2 (CCR2-64I) is associated with a delay in progression to AIDS in HIV-1-infected individuals. Our results suggest that an A isoform of CCR2 (CCR2A) binds to CCR5 in the cytoplasm and down-modulates its surface expression. We propose that the increased ability of CCR2A-64I to down-modulate CCR5 expression might be a possible cause of a delay in HIV-1 disease progression in patients with this allele.
3. The interleukin (IL)-4-589T allele bears a single nucleotide polymorphism at position・89 upstream from the open-reading frame of the IL-4 gene. Serum virus load was lower in patients with IL-4-589T than in those without this allele (P=0.02) in the French SEROCO cohort. Kaplan-Meier analysis survival curves showed a slower progression to clinical AIDS in carriers of IL-4-589T (P=0.04). These results suggest that IL-4-589T protects against HIV-1 disease progression by reducing virus load.
4. A total of 246 Thai female samples were genotyped for IL4 and RANTES promoter polymorphisms by PCR-RFLP. Our results implicate the significant protective effect of IL4-589T and RANTES-28G on HIV disease progression in Thais. In contrast, RANTES In1.1C without RANTES-28G had an accelerating effect on HIV disease progression.

Research Products

• [Journal Article] Protective Effects of IL-4-589T and RANTES-28G on HIV-1 disease progression in infected Thai females. (2006)
  • Author(s): Wichukchinda, N.
  • Journal Title: AIDS. 20 Pages: 189-196
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Effects of human interleukin 7 on HIV-1 replication in monocyte-derived human macrophages. (2006)
  • Author(s): Song, H.
  • Journal Title: AIDS. 20 Pages: 937-939
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Effects of human interleukin 7 on HIV-1 replication in monocyte-derived human macrophages. (2006)
  • Author(s): Song, H.
  • Journal Title: AIDS. (In press)
• [Journal Article] Influence of glycosylation on the efficacy of an Env-based vaccine against SIVmac239 in a macaque AIDS model. (2005)
  • Author(s): Mori, K.
  • Journal Title: J. Virol. 79 Pages: 10386-10396
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A specific region of 37 amino acid residues in the SPRY (B30.2) domain of African green monkey TRIM5α determines species-specific restriction of SIVmac infection. (2005)
  • Author(s): Nakayama, E. E.
  • Journal Title: J. Virol. 79 Pages: 8870-8877
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Influence of glycosylation on the efficacy of an Env-based vaccine against SIVmac239 in a macaque AIDS model. (2005)
  • Author(s): Mori, K.
  • Journal Title: J. Virol 79 Pages: 10386-10396
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A specific region of 37 amino acid residues in the SPRY (B30.2) domain of African green monkey TRIM5a determines species-specific restriction of SIVmac infection. (2005)
  • Author(s): Nakayama, E. E.
  • Journal Title: J. Virol. 79 Pages: 8870-8877
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Influence of glycosylation on the efficacy of an Env-based vaccine against SIVmac239 in a macaque AIDS model. (2005)
  • Author(s): Mori, K.
  • Journal Title: J.Virol. 79 Pages: 10386-10396
• [Journal Article] A specific region of 37 amino acid residues in the SPRY (B30.2) domain of African green monkey TRIM5 α determines species-specific restriction of SIVmac infection. (2005)
  • Author(s): Nakayama, E.E.
  • Journal Title: J.Virol. 79 Pages: 8870-8877
• [Journal Article] A specific region of 37 amino acid residues in the SPRY (B30.2) domain of African green monkey TRIM5 a determines species-specific restriction of SIVmac infection. (2005)
  • Author(s): Emi E.Nakayama, Hiroyuki Miyoshi, Yoshiyuki Nagai, Tatsuo Shioda
  • Journal Title: J.Virol. (in press)
• [Journal Article] A CCR2-V64I polymorphism affects stability of CCR2A isoform. (2004)
  • Author(s): Nakayama, E. E.
  • Journal Title: AIDS. 18 Pages: 729-738
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] A CCR2-V641 polymorphism affects stability of CCR2A isoform. (2004)
  • Author(s): Nakayama, E.E., Tanaka, Y., Nagai Y., Iwamoto, A., Shioda, T.
  • Journal Title: AIDS. 18 Pages: 729-738
• [Journal Article] Relationship between dimerization and packaging of HIV-1 genome RNA; a possible role of dimerization in genome packaging (2003)
  • Author(s): Sakuragi, J.
  • Journal Title: J. Virol 77 Pages: 4060-4069
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] No significant enhancement of protection by Tat-expressing Sendai viral vector-booster in a macaque AIDS model. (2003)
  • Author(s): Matano, T.
  • Journal Title: AIDS 17 Pages: 1392-1394
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Dissociation of genomic dimerization from packaging functions and virion maturation of human immunodeficiency virus type 1. (2002)
  • Author(s): Sakuragi, J.
  • Journal Title: J. Virol 76 Pages: 959-967
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Genetic analysis of HIV-1 discordant couples in Thailand : Association of CCR2 64I homozygosity with HIV-1 negative status. (2002)
  • Author(s): Louisirirotchanakul, S.
  • Journal Title: J. AIDS 29 Pages: 314-315
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Protective effect of IL4-589T polymorphism on HIV-1 disease progression : Relationship with viral load. (2002)
  • Author(s): Nakayama, E.E.
  • Journal Title: J. Infectious Diseases. 185 Pages: 1183-1186
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Maximal HIV-1 replication in alveolar macrophages during tuberculosis requires both lymphocyte contact and cytokines. (2002)
  • Author(s): Hoshino, Y.
  • Journal Title: J. Exp. Med. 195 Pages: 495-505
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Induction of HIV-1-Specific Neutralizing Antibodies in Mice Vaccinated with a Recombinant Sendai Virus Vector. (2002)
  • Author(s): Kano, M.
  • Journal Title: Jpn. J. Infect. Dis. 55 Pages: 59-60
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] An efficient and versatile mammalian viral vector system for major histocompatibility complex class I/peptide complexes. (2002)
  • Author(s): Kawana-Tachikawa, A.
  • Journal Title: J Virol 76 Pages: 11982-11988
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] New Rev-transport inhibitor with anti-HIV activity from Valerianae Radix. (2002)
  • Author(s): Murakami, N.
  • Journal Title: Bioorg Med Chem Lett 12 Pages: 2807-2810
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Dissociation of genomic dimerization from packaging functions and virion maturation of human immunodeficiecny virus type 1. (2002)
  • Author(s): Sakuragi, J.
  • Journal Title: J. Virol. 76 Pages: 959-967
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Genetic analysis of HIV-1 discordant couples in Thailand : Association of CCR2 641 homozygosity with HIV-1 negative status. (2002)
  • Author(s): Louisirirotchanakul, S.
  • Journal Title: J. AIDS 29 Pages: 314-315
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Protective effect of IL4-589T polymorphism on HIV-1 disease progression : Relationship with viral load. (2002)
  • Author(s): Nakayama, E.E.
  • Journal Title: J.Infectious Dis. 185 Pages: 1183-1186
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Induction of HIV-1-Specific Neutralizing Antibodies in Mice Vaccinated with a Recombinant Sendai Virus Vector (2002)
  • Author(s): Kano, M.
  • Journal Title: Jpn. J. Infect. Dis. 55 Pages: 59-60
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] A An efficient and versatile mammalian viral vector system for major histocompatibility complex class I/peptide complexes (2002)
  • Author(s): Kawana-Tachikawa
  • Journal Title: J Virol 76 Pages: 11982-11988
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Jun-Ichi Sakuragi, Shigeharu Ueda, Aikichi Iwamoto, Tatsuo Shioda: "Relationship between dimerization and packaging of HIV-1 genome RNA ; a possible role of dimerization in genome packaging."J.Virol.. 77. 4060-4069 (2003)
• [Publications] Matano T, Kano M, Takeda A, Nakamura H, Nomura N, Furuta Y, Shioda T, Nagai Y: "No significant enhancement of protection by Tat-expressing Sendai viral vector-booster in a macaque AIDS model."AIDS. 17. 1392-1394 (2003)
• [Publications] Nakayama, E.E., Tanaka, Y., Nagai, Y., Iwamoto, A., Shioda T.: "A CCR2-V64I polymorphism affects stability of CCR2A isoform."AIDS. 18(In press). (2004)
• [Publications] Jun-ichi Sakuragi, Aikichi Iwamoto, Tatsuo Shioda: "Dissociation of genomic dimerization from packaging functions and virion maturation of human immunodeficiecny virus type 1"J. Virol.. 76. 959-967 (2002)
• [Publications] Suda Louisirirotchanakul, Huanliang Liu, Anuvat Roongpisuthipong, Emi E.Nakayama, Yutaka Takebe, Tatsuo Shioda, Chantapong Wasi.: "Genetic analysis of HIV-1 discordant couples in Thailand : Association of CCR2 64I homozygosity with HIV-1 negative status"J. AIDS.. 29. 314-315 (2002)
• [Publications] Emi E.Nakayama, Laurence Meyer, Aikichi Iwamoto, Anne Persoz, Yoshiyuki Nagai, Christine Rouzioux, Jean-Francois Delfraissy, SEROCO Study Group, Patrice Debre, Dorian Mcllroy, Ioannis Theodorou, Tatsuo Shioda: "Protective effect of IL4 -589T polymorphism on HIV-1 disease progress Relationship with viral load"J. Infectious Diseases.. 185. 1183-1186 (2002)
• [Publications] Yoshihiko Hoshino, Koh Nakata, Satomi Hoshino, Yoshihiro Honda, Doris Tse, Tatsuo Shioda, William N.Rom, Michael Weiden: "Maximal HIV-1 replication in alveolar macrophages during tuberculosis requires both lymphocyte contact and cytokines"J. Exp. Med.. 195. 495-505 (2002)
• [Publications] Munehide Kano, Tetsuo Matano, Atsushi Kato, Tatsuo Shioda, Yoshiyuki Nagai: "Induction of HIV-1-Specific Neutralizing Antibodies in Mice Vaccinated with a Recombinant Sendai Virus Vector"Jpn. J. Infect. Dis.. 55. 59-60 (2002)
• [Publications] Kawana-Tachikawa A, Tomizawa M, Nunoya J, Shioda T, Kato A, Nakayama EE, Nakamura T, Nagai Y, Iwamoto A: "An efficient and versatile mammalian viral vector system for major histocompatibility complex class I/peptide complexes"J Virol. 76. 11982-11988 (2002)
• [Publications] Murakami N, Ye Y, Kawanishi M, Aoki S, Kudo N, Yoshida M, Nakayama EE, Shioda T, Kobayashi M.: "New Rev-transport inhibitor with anti-HIV activity from Valerianae Radix"Bioorg Med Chem Lett. 12. 2807-2810 (2002)
• [Publications] Jun-Ichi Sakuragi, Shigeharu Ueda, Aikichi Iwamoto, Tatsuo Shioda: "Relationship between dimerization and packaging of HIV-1 genome RNA ; a possible role of dimerization in genome packaging"J. Virol. (In press). (2003)