title: Identification of SNF2h, a chromatin-remodeling factor, as a novel binding protein of Vpr of human immunodeficiency virus type 1.
abstract: Vpr, an accessory gene of human immunodeficiency virus type 1, encodes a virion-associated nuclear protein that plays an important role in the primary viral infection of resting macrophages. It has a variety of biological functions, including roles in a cell cycle abnormality at G(2)/M phase, apoptosis, nuclear transfer of preintegration complex, and DNA double-strand breaks (DSBs), some of which depend on its association with the chromatin of the host cells. Given that DSB signals are postulated to be a positive factor in the viral infection, understanding the mode of chromatin recruitment of Vpr is important. Here, we identified SNF2h, a chromatin-remodeling factor, as a novel binding partner of Vpr involved in its chromatin recruitment. When endogenous SNF2h protein was extensively downregulated by SNF2h small interfering RNA (siRNA), the amount of Vpr loaded on chromatin decreased to about 30% of the control level. Biochemical analysis using a mutant Vpr suggested that Vpr binds SNF2h via HFRIG (amino acids 71-75 depicted by single letters) and the Vpr mutant lacking this motif lost the activity to induce DSB-dependent signals. Consistently, Vpr-induced DSBs were attenuated by extensive downregulaion of endogenous SNF2h. Based on these data, we discuss the role of DSB and DSB signals in the viral infection.
authors.affiliation: Department of Intractable Diseases, National Center for Global Health and Medicine, 1-21-1 Toyama, Shinjuku, Tokyo 162-8655, Japan.
authors.forename: Daiki
authors.initials: D
authors.lastname: Taneichi
authors.forename: Kenta
authors.initials: K
authors.lastname: Iijima
authors.forename: Akihiro
authors.initials: A
authors.lastname: Doi
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Koyama
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Minemoto
authors.forename: Kenzo
authors.initials: K
authors.lastname: Tokunaga
authors.forename: Mari
authors.initials: M
authors.lastname: Shimura
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Kano
authors.forename: Yukihito
authors.initials: Y
authors.lastname: Ishizaka
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000235:genetics / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D057809:HEK293 Cells; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D011485:Protein Binding / Q000235:genetics; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D054325:vpr Gene Products, Human Immunodeficiency Virus; D000251:Adenosine Triphosphatases; C409462:SMARCA5 protein, human