Mutational analysis of human immunodeficiency virus type 1 (HIV-1) accessory genes: Requirement of a site in the nef gene for HIV-1 replication in activated CD4+ T cells in vitro and in vivo

Yuji Kawano, Yuetsu Tanaka, Naoko Misawa, Reiko Tanaka, Jun-Ichi Kira, Tohru Kimura, Masaya Fukushi, Kouichi Sano, Toshiyuki Goto, Masuyo Nakai, Takuro Kobayashi, Naoki Yamamoto, Yoshio Koyanagi

研究成果: ジャーナルへの寄稿記事

45 引用 (Scopus)

抄録

Human immunodeficiency virus type 1 (HIV-1) accessory genes including nef, vif, and vpr are important factors that determine the replication and pathogenesis of HIV-1. The state of activation is also important for the replication of HIV-1. We evaluated the properties of nef-, vif-, and vpr- minus macrophage-tropic HIV-1(JR-) CSF in primary CD4+ Th1- or Th2-like cell cultures which had been activated through CD3 molecules in the presence of interleukin-2 (IL-2) and IL-12 (Th1-like culture) or IL-4 (Th2-like culture), respectively. In activated Th1- or Th2-like cultures, replication of nef- minus HIV-1(JR-CSF) was markedly lower than that of wild-type HIV-1. Subsequent analysis by site-directed mutagenesis showed that (i) the presence or an acidic amino acid-rich domain (amino acid residues 72 to 75) in the Nef protein was critical for the enhancement of viral DNA synthesis, resulting in increased virus growth rate, and (ii) prolines that form part of Src homology 3 binding domain were not essential for viral replication. We also confirmed the importance of sites by using an HIV-1-infected animal model, the hu-PBL- SCID mouse system, representing HIV-1 replication and pathogenesis in activated CD4+ T cells in vivo. These results indicate that Nef accelerates viral replication in activated CD4+ T cells.

元の言語英語
ページ(範囲)8456-8466
ページ数11
ジャーナルJournal of virology
71
発行部数11
出版物ステータス出版済み - 11 1 1997

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nef Genes
Virus Replication
Human immunodeficiency virus 1
HIV-1
T-lymphocytes
T-Lymphocytes
Genes
genes
virus replication
pathogenesis
nef Gene Products
Acidic Amino Acids
Th2 Cells
amino acids
SCID Mice
In Vitro Techniques
interleukin-12
site-directed mutagenesis
Viral DNA
interleukin-4

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

これを引用

Mutational analysis of human immunodeficiency virus type 1 (HIV-1) accessory genes : Requirement of a site in the nef gene for HIV-1 replication in activated CD4+ T cells in vitro and in vivo. / Kawano, Yuji; Tanaka, Yuetsu; Misawa, Naoko; Tanaka, Reiko; Kira, Jun-Ichi; Kimura, Tohru; Fukushi, Masaya; Sano, Kouichi; Goto, Toshiyuki; Nakai, Masuyo; Kobayashi, Takuro; Yamamoto, Naoki; Koyanagi, Yoshio.

:: Journal of virology, 巻 71, 番号 11, 01.11.1997, p. 8456-8466.

研究成果: ジャーナルへの寄稿記事

Kawano, Y, Tanaka, Y, Misawa, N, Tanaka, R, Kira, J-I, Kimura, T, Fukushi, M, Sano, K, Goto, T, Nakai, M, Kobayashi, T, Yamamoto, N & Koyanagi, Y 1997, 'Mutational analysis of human immunodeficiency virus type 1 (HIV-1) accessory genes: Requirement of a site in the nef gene for HIV-1 replication in activated CD4+ T cells in vitro and in vivo', Journal of virology, 巻. 71, 番号 11, pp. 8456-8466.
Kawano, Yuji ; Tanaka, Yuetsu ; Misawa, Naoko ; Tanaka, Reiko ; Kira, Jun-Ichi ; Kimura, Tohru ; Fukushi, Masaya ; Sano, Kouichi ; Goto, Toshiyuki ; Nakai, Masuyo ; Kobayashi, Takuro ; Yamamoto, Naoki ; Koyanagi, Yoshio. / Mutational analysis of human immunodeficiency virus type 1 (HIV-1) accessory genes : Requirement of a site in the nef gene for HIV-1 replication in activated CD4+ T cells in vitro and in vivo. :: Journal of virology. 1997 ; 巻 71, 番号 11. pp. 8456-8466.
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abstract = "Human immunodeficiency virus type 1 (HIV-1) accessory genes including nef, vif, and vpr are important factors that determine the replication and pathogenesis of HIV-1. The state of activation is also important for the replication of HIV-1. We evaluated the properties of nef-, vif-, and vpr- minus macrophage-tropic HIV-1(JR-) CSF in primary CD4+ Th1- or Th2-like cell cultures which had been activated through CD3 molecules in the presence of interleukin-2 (IL-2) and IL-12 (Th1-like culture) or IL-4 (Th2-like culture), respectively. In activated Th1- or Th2-like cultures, replication of nef- minus HIV-1(JR-CSF) was markedly lower than that of wild-type HIV-1. Subsequent analysis by site-directed mutagenesis showed that (i) the presence or an acidic amino acid-rich domain (amino acid residues 72 to 75) in the Nef protein was critical for the enhancement of viral DNA synthesis, resulting in increased virus growth rate, and (ii) prolines that form part of Src homology 3 binding domain were not essential for viral replication. We also confirmed the importance of sites by using an HIV-1-infected animal model, the hu-PBL- SCID mouse system, representing HIV-1 replication and pathogenesis in activated CD4+ T cells in vivo. These results indicate that Nef accelerates viral replication in activated CD4+ T cells.",
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AU - Kawano, Yuji

AU - Tanaka, Yuetsu

AU - Misawa, Naoko

AU - Tanaka, Reiko

AU - Kira, Jun-Ichi

AU - Kimura, Tohru

AU - Fukushi, Masaya

AU - Sano, Kouichi

AU - Goto, Toshiyuki

AU - Nakai, Masuyo

AU - Kobayashi, Takuro

AU - Yamamoto, Naoki

AU - Koyanagi, Yoshio

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