SOCS1 is an inducible host factor during HIV-1 infection and regulates the intracellular trafficking and stability of HIV-1 Gag

被引：63

作者：

Ryo, Akihide ^{[1
,2
]}

Tsurutan, Naomi ^{[3
]}

Ohba, Kenji ^{[2
,4
]}

Kimura, Ryuichiro ^{[4
]}

Komano, Jun ^{[2
]}

Nishi, Mayuko ^{[1
]}

Soeda, Hiromi ^{[1
]}

Hattori, Shinichiro ^{[2
]}

Perrem, Kilian ^{[7
]}

Yamamoto, Mikio ^{[6
]}

Chiba, Joe ^{[5
]}

Mimaya, Jun-Ichi ^{[8
]}

Yoshimura, Kazuhisa ^{[9
]}

Matsushita, Shuzo ^{[9
]}

Honda, Mitsuo

Yoshimura, Akihiko ^{[10
]}

Sawasaki, Tatsuya ^{[11
]}

Aoki, Ichiro ^{[1
]}

Morikawa, Yuko ^{[3
]}

Yamamoto, Naoki ^{[2
]}

机构：

[1] Yokohama City Univ, Sch Med, Dept Pathol, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan

[2] Natl Inst Infect Dis, AIDS Res Ctr, Shinjuku Ku, Tokyo 1628640, Japan

[3] Kitasato Univ, Kitasato Inst Life Sci, Minato Ku, Tokyo 1088641, Japan

[4] Tokyo Med & Dent Univ, Dept Mol Virol, Grad Sch Med, Bunkyo Ku, Tokyo 1138519, Japan

[5] Royal Coll Surgeons Ireland, Dept Pathol, Mol Oncol Lab, Dublin 9, Ireland

[6] Natl Def Med Coll, Dept Biochem 2, Tokorozawa, Saitama 3598513, Japan

[7] Tokyo Univ Sci, Dept Biol Sci & Technol, Chiba 2788510, Japan

[8] Shizuoka Childrens Hosp, Div Hematol & Oncol, Aoi Ku, Shizuoka 4208660, Japan

[9] Kumamoto Univ, Grad Sch Med Sci, Ctr AIDS Res, Div Clin Retrovirol & Infect Dis, Kumamoto 8600811, Japan

[10] Kyushu Univ, Med Inst Bioregulat, Div Mol & Cellular Immunol, Fukuoka 8128582, Japan

[11] Ehime Univ, Cell Free Sci & Res Ctr, Matsuyama, Ehime 7908577, Japan

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2008年 / 105卷 / 01期

关键词：

AIDS; pathogenesis; drug target; lysozyme;

D O I：

10.1073/pnas.0704831105

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Human immunodeficiency virus type 1 (HIV-1) utilizes the macromolecular machinery of the infected host cell to produce progeny virus. The discovery of cellular factors that participate in HIV-1 replication pathways has provided further insight into the molecular basis of virus-host cell interactions. Here, we report that the suppressor of cytokine signaling 1 (SOCS1) is an inducible host factor during HIV-1 infection and regulates the late stages of the HIV-1 replication pathway. SOCS1 can directly bind to the matrix and nucleocapsid regions of the HIV-1 p55 Gag polyprotein and enhance its stability and trafficking, resulting in the efficient production of HIV-1 particles via an IFN signaling-independent mechanism. The depletion of SOCS1 by siRNA reduces both the targeted trafficking and assembly of HIV-1 Gag, resulting in its accumulation as perinuclear solid aggregates that are eventually subjected to lysosomal degradation. These results together indicate that SOCS1 is a crucial host factor that regulates the intracellular dynamism of HIV-1 Gag and could therefore be a potential new therapeutic target for AIDS and its related disorders.

引用

页码：294 / 299

页数：6

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