title: SOCS1 is an inducible host factor during HIV-1 infection and regulates the intracellular trafficking and stability of HIV-1 Gag.
abstract: 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.
authors.affiliation: Department of Pathology, Yokohama City University School of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236-0004, Japan. aryo@nih.go.jp
authors.forename: Akihide
authors.initials: A
authors.lastname: Ryo
authors.forename: Naomi
authors.initials: N
authors.lastname: Tsurutani
authors.forename: Kenji
authors.initials: K
authors.lastname: Ohba
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Kimura
authors.forename: Jun
authors.initials: J
authors.lastname: Komano
authors.forename: Mayuko
authors.initials: M
authors.lastname: Nishi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Soeda
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Hattori
authors.forename: Kilian
authors.initials: K
authors.lastname: Perrem
authors.forename: Mikio
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Joe
authors.initials: J
authors.lastname: Chiba
authors.forename: Jun-Ichi
authors.initials: J
authors.lastname: Mimaya
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Shuzo
authors.initials: S
authors.lastname: Matsushita
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Honda
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sawasaki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Aoki
authors.forename: Yuko
authors.initials: Y
authors.lastname: Morikawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
mesh_terms: 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
chemical_list: 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