2000 Fiscal Year Annual Research Report

HIV-1感染時の細胞活性化状態とその後のウイルス存在様式

Research Project

Project/Area Number	12035214
Research Institution	Osaka University
Principal Investigator	生田和良大阪大学, 微生物病研究所, 教授 (60127181)
Keywords	HIV-1 / ウイルストロピズム / AIDS病態 / CD4 / CD38 / CCR5 / CXCR4 / 細胞活性化
Research Abstract	AIDS病態はプラズマウイルス負荷と密接な相関関係にあり、AIDS病態の進行とともにマクロファージ指向性HIV-1からT細胞指向性HIV-1へとウイルストロピズムもシフトすることが知られている。一方、HIV-1感染者には免疫T細胞のうち、CD38抗原を発現している細胞の割合が上昇することから、病態マーカーのひとつとして用いられている。そこで、私たちはHIV-1感染者にみられるCD4+CD38+T細胞の割合が上昇する点に着目して、CD4+T細胞のCD38+のサブセットとCD38-サブセットがHIV-1の感受性に違いを見せる可能性について検討した。その結果、CD38+のサブセットはT細胞指向性HIV-1に高感受はを示し、逆にCD38-サブセットはマクロファージ指向性HIV-1に高感受はを示すことが判明した。次に、それぞれの高感受性を示す機序を検討した。CD38+サブセットとCD38-サブセット間でHIV-1レセプターであるCD4の発現には差異が認められなかった。CD38-サブセットはCD38+サブセットに比べ、マクロファージ指向性HIV-1のコレセプターであるCCR5発現が高かった。一方、T細胞指向性HIV-1のコレセプターであるCXCR4は両サブセットで顕著な違いが認められなかった。そこで、サイトカイン分泌能について検討したところ、CD38+サブセットはTh2サイトカインであるIL-4を高分泌しており、このIL-4がこのサブセットでのT細胞指向性HIV-1の高感受性に関わっていることが明らかとなった。したがって、AIDS病態進行とともに変化するT細胞サブセットの変化がHIV-1のトロピズムのシフトという結果を招いていると考えられる。

Research Products

(10 results)

All Other

All Publications (10 results)

[Publications] Auwanit,W.,Ikuta,K. et al.: "Highly variable sequences at env V3 region of HIV-1 distributing among Thai carriers during 1995 to 1997."AIDS Res.Human Retroviruses. 16. 283-289 (2000)
[Publications] Bahmani,M.K.,Ikuta,K. et al.: "Fusion of uninfected T-cells occurs with immature HIV-1 protease-mutant, but not morphologically similar protease inhibitor derived particles."Virus Research. 66. 131-137 (2000)
[Publications] Zheng,YH.,Ikuta,K. et al.: "Mutations occurring during serial passage of Japanese equine infectious anemia virus in primary horse macrophages"Virus Research. 68. 93-98 (2000)
[Publications] Zheng,YH.,Ikuta,K. et al.: "Replication ability in vitro and in vivo of equine infectious anemia virus avirulent Japanese strain."Virology. 266. 129-139 (2000)
[Publications] Suzuki,S.,Ikuta,K. et al.: "Exposure of normal monocyte-derived dendritic cells to human immunodeficiency virus type-1 particles leads to the induction of apoptosis in co-cultured CD4^+ as well as CD8^+ T cells."Microbiol.Immunol.. 44. 111-121 (2000)
[Publications] Ikuta,K.,Suzuki,S. et al.: "Positive and negative aspects of the human immunodeficiency virus protease : development of inhibitors versus its role in AIDS pathogenesis."Microbiol.Mol.Biol.Rev.(MMBR). 64. 725-745 (2000)
[Publications] Horikoshi,H.,Ikuta,K. et al.: "Differential susceptibility of resting CD4^+ T lymphocytes by their surface expression of CD38 to T-cell-tropic and macrophage-tropic human immunodeficiency virus type 1."Virus Res.. 73. 1-16 (2001)
[Publications] Komoto,S.,Ikuta,K. et al.: "Low or no antibody responses to human immunodeficiency virus type 1 Nef in infected carriers with subtype E, in contrast to subtype B that showed antibodies preferentially recognizing subtype-specific Nef epitopes."Vaccine. (in press).
[Publications] Kurosu,T.,Ikuta,K. et al.: "Variable sequences in the long terminal repeat and its downstream region of some od HIV-1 CRF01_AE recentry distributing among Thai Carriers"AIDS Res.Hum.Retroviruses. (in press).
[Publications] Auwanit,W.,Ikuta,K. et al.: "Full-length sequences of two CRF01_AE (subtype E) HIV-1 isolates from 1995 samples of patients with sexually transmitted diseases in Thailand."AIDS Res.Hum.Retroviruses. (in press).

2000 Fiscal Year Annual Research Report

HIV-1感染時の細胞活性化状態とその後のウイルス存在様式

Principal Investigator

生田 和良 大阪大学, 微生物病研究所, 教授 (60127181)

Research Products

[Publications] Auwanit,W.,Ikuta,K. et al.: "Highly variable sequences at env V3 region of HIV-1 distributing among Thai carriers during 1995 to 1997."AIDS Res.Human Retroviruses. 16. 283-289 (2000)

[Publications] Bahmani,M.K.,Ikuta,K. et al.: "Fusion of uninfected T-cells occurs with immature HIV-1 protease-mutant, but not morphologically similar protease inhibitor derived particles."Virus Research. 66. 131-137 (2000)

[Publications] Zheng,YH.,Ikuta,K. et al.: "Mutations occurring during serial passage of Japanese equine infectious anemia virus in primary horse macrophages"Virus Research. 68. 93-98 (2000)

[Publications] Zheng,YH.,Ikuta,K. et al.: "Replication ability in vitro and in vivo of equine infectious anemia virus avirulent Japanese strain."Virology. 266. 129-139 (2000)

[Publications] Suzuki,S.,Ikuta,K. et al.: "Exposure of normal monocyte-derived dendritic cells to human immunodeficiency virus type-1 particles leads to the induction of apoptosis in co-cultured CD4^+ as well as CD8^+ T cells."Microbiol.Immunol.. 44. 111-121 (2000)

[Publications] Ikuta,K.,Suzuki,S. et al.: "Positive and negative aspects of the human immunodeficiency virus protease : development of inhibitors versus its role in AIDS pathogenesis."Microbiol.Mol.Biol.Rev.(MMBR). 64. 725-745 (2000)

[Publications] Horikoshi,H.,Ikuta,K. et al.: "Differential susceptibility of resting CD4^+ T lymphocytes by their surface expression of CD38 to T-cell-tropic and macrophage-tropic human immunodeficiency virus type 1."Virus Res.. 73. 1-16 (2001)

[Publications] Komoto,S.,Ikuta,K. et al.: "Low or no antibody responses to human immunodeficiency virus type 1 Nef in infected carriers with subtype E, in contrast to subtype B that showed antibodies preferentially recognizing subtype-specific Nef epitopes."Vaccine. (in press).

[Publications] Kurosu,T.,Ikuta,K. et al.: "Variable sequences in the long terminal repeat and its downstream region of some od HIV-1 CRF01_AE recentry distributing among Thai Carriers"AIDS Res.Hum.Retroviruses. (in press).

[Publications] Auwanit,W.,Ikuta,K. et al.: "Full-length sequences of two CRF01_AE (subtype E) HIV-1 isolates from 1995 samples of patients with sexually transmitted diseases in Thailand."AIDS Res.Hum.Retroviruses. (in press).

生田和良大阪大学, 微生物病研究所, 教授 (60127181)