Mutational analysis of HIV-2 Vpx shows that proline residue 109 in the poly-proline motif regulates degradation of SAMHD1

被引:10
作者
Ciftci, Halil Ibrahim [1 ]
Fujino, Haruna [1 ]
Koga, Ryoko [1 ]
Yamamoto, Minami [1 ]
Kawamura, Sogo [1 ]
Tateishi, Hiroshi [1 ]
Iwatani, Yasumasa [2 ]
Otsuka, Masami [1 ]
Fujita, Mikako [3 ]
机构
[1] Kumamoto Univ, Fac Life Sci, Dept Bioorgan Med Chem, Kumamoto, Japan
[2] Natl Hosp Org, Nagoya Med Ctr, Clin Res Ctr, Nagoya, Aichi, Japan
[3] Kumamoto Univ, Sch Pharm, Res Inst Drug Discovery, Kumamoto, Japan
基金
日本学术振兴会;
关键词
HIV-2; Vpx; SAMHD1; Poly-proline; IMMUNODEFICIENCY-VIRUS TYPE-1; AICARDI-GOUTIERES SYNDROME; RESTRICTION FACTOR SAMHD1; VIRAL INFECTIVITY; PROTEIN; REPLICATION; GENE; VIF; ASSOCIATION; EXPRESSION;
D O I
10.1016/j.febslet.2015.04.038
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
In this study, we performed a mutational analysis to determine whether the mechanism by which HIV-2 Vpx confers the capacity for infectivity and viral replication in macrophages is solely dependent on its ability to degrade the host antiviral factor SAMHD1. Contrary to expectations, we demonstrated that P109 in the C-terminal poly-proline motif of HIV-2 Vpx has two unique roles: to facilitate the specific degradation of SAMHD1 in macrophages, and to facilitate multimerization of Vpx, therefore preventing SAMHD1 degradation in the presence of high levels of Vpx. (C) 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:1505 / 1514
页数:10
相关论文
共 58 条
[1]   A conserved dileucine-containing motif in p6gag governs the particle association of Vpx and Vpr of simian immunodeficiency viruses SIVmac and SIVagm [J].
Accola, MA ;
Bukovsky, AA ;
Jones, MS ;
Gottlinger, HG .
JOURNAL OF VIROLOGY, 1999, 73 (12) :9992-9999
[2]   PRODUCTION OF ACQUIRED IMMUNODEFICIENCY SYNDROME-ASSOCIATED RETROVIRUS IN HUMAN AND NONHUMAN CELLS TRANSFECTED WITH AN INFECTIOUS MOLECULAR CLONE [J].
ADACHI, A ;
GENDELMAN, HE ;
KOENIG, S ;
FOLKS, T ;
WILLEY, R ;
RABSON, A ;
MARTIN, MA .
JOURNAL OF VIROLOGY, 1986, 59 (02) :284-291
[3]   Nuclease Activity of the Human SAMHD1 Protein Implicated in the Aicardi-Goutieres Syndrome and HIV-1 Restriction [J].
Beloglazova, Natalia ;
Flick, Robert ;
Tchigvintsev, Anatoli ;
Brown, Greg ;
Popovic, Ana ;
Nocek, Boguslaw ;
Yakunin, Alexander F. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (12) :8101-8110
[4]   Vpx is Critical for SIVmne infection of pigtail macaques [J].
Belshan, Michael ;
Kimata, Jason T. ;
Brown, Charles ;
Cheng, Xiaogang ;
McCulley, Anna ;
Larsen, Alison ;
Thippeshappa, Rajesh ;
Hodara, Vida ;
Giavedoni, Luis ;
Hirsch, Vanessa ;
Ratner, Lee .
RETROVIROLOGY, 2012, 9
[5]   The Human Immunodeficiency Virus Type 2 Vpx Protein Usurps the CUL4A-DDB1DCAF1 Ubiquitin Ligase To Overcome a Postentry Block in Macrophage Infection [J].
Bergamaschi, Anna ;
Ayinde, Diana ;
David, Annie ;
Le Rouzic, Erwann ;
Morel, Marina ;
Collin, Gilles ;
Descamps, Diane ;
Damond, Florence ;
Brun-Vezinet, Francoise ;
Nisole, Sebastien ;
Margottin-Goguet, Florence ;
Pancino, Gianfranco ;
Transy, Catherine .
JOURNAL OF VIROLOGY, 2009, 83 (10) :4854-4860
[6]   Functional Analysis of the Relationship between Vpx and the Restriction Factor SAMHD1 [J].
Berger, Gregory ;
Turpin, Jocelyn ;
Cordeil, Stephanie ;
Tartour, Kevin ;
Nguyen, Xuan-Nhi ;
Mahieux, Renaud ;
Cimarelli, Andrea .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (49) :41210-41217
[7]   Identification of highly attenuated mutants of simian immunodeficiency virus [J].
Desrosiers, RC ;
Lifson, JD ;
Gibbs, JS ;
Czajak, SC ;
Howe, AYM ;
Arthur, LO ;
Johnson, RP .
JOURNAL OF VIROLOGY, 1998, 72 (02) :1431-1437
[8]   Nuclear import and cell cycle arrest functions of the HIV-1 Vpr protein are encoded by two separate genes in HIV-2/SIVSM [J].
Fletcher, TM ;
Brichacek, B ;
Sharova, N ;
Newman, MA ;
Stivahtis, G ;
Sharp, PM ;
Emerman, M ;
Hahn, BH ;
Stevenson, M .
EMBO JOURNAL, 1996, 15 (22) :6155-6165
[9]   Expression of HIV-1 accessory protein Vif is controlled uniquely to be low and optimal by proteasome degradation [J].
Fujita, M ;
Akari, H ;
Sakurai, A ;
Yoshida, A ;
Chiba, T ;
Tanaka, K ;
Strebel, K ;
Adachi, A .
MICROBES AND INFECTION, 2004, 6 (09) :791-798
[10]   Amino acid residues 88 and 89 in the central hydrophilic region of human immunodeficiency virus type 1 Vif are critical for viral infectivity by enhancing the steady-state expression of Vif [J].
Fujita, M ;
Sakurai, A ;
Yoshida, A ;
Miyaura, M ;
Koyama, AH ;
Sakai, K ;
Adachi, A .
JOURNAL OF VIROLOGY, 2003, 77 (02) :1626-1632