SOCS1 is an inducible host factor during HIV-1 infection and regulates the intracellular trafficking and stability of HIV-1 Gag.
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.
Ryo
Akihide
A
Department of Pathology, Yokohama City University School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan. aryo@nih.go.jp
Tsurutani
Naomi
N
Ohba
Kenji
K
Kimura
Ryuichiro
R
Komano
Jun
J
Nishi
Mayuko
M
Soeda
Hiromi
H
Hattori
Shinichiro
S
Perrem
Kilian
K
Yamamoto
Mikio
M
Chiba
Joe
J
Mimaya
Jun-Ichi
J
Yoshimura
Kazuhisa
K
Matsushita
Shuzo
S
Honda
Mitsuo
M
Yoshimura
Akihiko
A
Sawasaki
Tatsuya
T
Aoki
Ichiro
I
Morikawa
Yuko
Y
Yamamoto
Naoki
N
D000163:Acquired Immunodeficiency Syndrome / Q000628:therapy; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D015683:Gene Products, gag / Q000378:metabolism*; D015658:HIV Infections / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D008854:Microscopy, Electron; D046529:Microscopy, Electron, Transmission; D009113:Muramidase / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D012323:RNA Processing, Post-Transcriptional; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000378:metabolism / Q000502:physiology*; D014779:Virus Replication
D015683:Gene Products, gag; D034741:RNA, Small Interfering; C108944:SOCS1 protein, human; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D009113:Muramidase