Daxx Inhibits HIV-1 Reverse Transcription and Uncoating in a SUMO-Dependent Manner

被引:15
|
作者
Maillet, Sarah [1 ]
Fernandez, Juliette [1 ]
Decourcelle, Mathilde [2 ]
El Koulali, Khadija [2 ]
Blanchet, Fabien P. [1 ]
Arhel, Nathalie J. [1 ]
Maarifi, Ghizlane [1 ]
Nisole, Sebastien [1 ]
机构
[1] Univ Montpellier, Inst Rech Infectiol Montpellier IRIM, CNRS, F-34090 Montpellier, France
[2] Univ Montpellier, INSERM, CNRS, BCM, F-34090 Montpellier, France
来源
VIRUSES-BASEL | 2020年 / 12卷 / 06期
关键词
Daxx; HIV-1; reverse transcription; uncoating; restriction factor; interferon; ISG; intrinsic immunity; host defense; IMMUNODEFICIENCY-VIRUS TYPE-1; NUCLEAR IMPORT; CYCLOPHILIN-A; PROTEIN DAXX; EARLY STEPS; TRIM5-ALPHA; RESTRICTION; INFECTION; REPLICATION; REPRESSION;
D O I
10.3390/v12060636
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Death domain-associated protein 6 (Daxx) is a multifunctional, ubiquitously expressed and highly conserved chaperone protein involved in numerous cellular processes, including apoptosis, transcriptional repression, and carcinogenesis. In 2015, we identified Daxx as an antiretroviral factor that interfered with HIV-1 replication by inhibiting the reverse transcription step. In the present study, we sought to unravel the molecular mechanism of Daxx-mediated restriction and, in particular, to identify the protein(s) that Daxx targets in order to achieve its antiviral activity. First, we show that the SUMO-interacting motif (SIM) located at the C-terminus of the protein is strictly required for Daxx to inhibit HIV-1 reverse transcription. By performing a quantitative proteomic screen combined with classical biochemical analyses, we found that Daxx associated with incoming HIV-1 cores through a SIM-dependent interaction with cyclophilin A (CypA) and capsid (CA). Daxx was found to reside within a multiprotein complex associated with viral capsids, also containing TNPO3, TRIM5 alpha, and TRIM34. Given the well-known influence of these cellular factors on the stability of HIV-1 cores, we investigated the effect of Daxx on the cytoplasmic fate of incoming cores and found that Daxx prevented HIV-1 uncoating in a SIM-dependent manner. Altogether, our findings suggest that, by recruiting TNPO3, TRIM5 alpha, and TRIM34 and possibly other proteins onto incoming HIV-1 cores through a SIM-dependent interaction with CA-bound CypA, Daxx increases their stability, thus preventing uncoating and reverse transcription. Our study uncovers a previously unknown function of Daxx in the early steps of HIV-1 infection and further illustrates how reverse transcription and uncoating are two tightly interdependent processes.
引用
收藏
页数:19
相关论文
共 50 条
  • [31] Role of HIV-1 nucleocapsid protein in HIV-1 reverse transcription
    Levin, Judith G.
    Mitra, Mithun
    Mascarenhas, Anjali
    Musier-Forsyth, Karin
    RNA BIOLOGY, 2010, 7 (06) : 754 - 774
  • [32] SUMO-dependent regulation of the yeast transcription factor Cin5
    Park, S.
    Kitazono, A.
    MOLECULAR BIOLOGY OF THE CELL, 2012, 23
  • [33] Revisiting HIV-1 uncoating
    Arhel, Nathalie
    RETROVIROLOGY, 2010, 7
  • [34] Daxx interacts with HIV-1 integrase and inhibits lentiviral gene expression
    Huang, Lu
    Xu, Guan-lan
    Zhang, Jian-qi
    Tian, Ling
    Xue, Jing-lun
    Chen, Jin-zhong
    Jia, William
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2008, 373 (02) : 241 - 245
  • [35] Natural endogenous reverse transcription of HIV-1
    Zhang, H
    Dornadula, G
    Pomerantz, RJ
    JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 1998, 41 (1-2) : 255 - 260
  • [36] Cellular factors and HIV-1 reverse transcription
    Warren, K.
    Wei, T.
    Li, D. S.
    Warrilow, D.
    Harrich, D.
    INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, 2011, 15 : S37 - S37
  • [37] HIV-1 ENTRY AND REVERSE TRANSCRIPTION IN MACROPHAGES
    OBRIEN, WA
    JOURNAL OF LEUKOCYTE BIOLOGY, 1994, 56 (03) : 273 - 277
  • [38] The small molecule 3G11 inhibits HIV-1 reverse transcription
    Fricke, Thomas
    Opp, Silvana
    Shepard, Caitlin
    Ivanov, Dmitri
    Kim, Baek
    Valle-Casuso, Jose
    Diaz-Griffero, Felipe
    RETROVIROLOGY, 2016, 13
  • [39] HIV-1 Uncoating Occurs via a Series of Rapid Biomechanical Changes in the Core Related to Individual Stages of Reverse Transcription
    Rankovic, Sanela
    Deshpande, Akshay
    Harel, Shimon
    Aiken, Christopher
    Rousso, Itay
    JOURNAL OF VIROLOGY, 2021, 95 (10)
  • [40] HIV-1 Uncoating and Reverse Transcription Require eEF1A Binding to Surface-Exposed Acidic Residues of the Reverse Transcriptase Thumb Domain
    Rawle, Daniel J.
    Li, Dongsheng
    Swedberg, Joakim E.
    Wang, Lu
    Soares, Dinesh C.
    Harrich, David
    MBIO, 2018, 9 (02):