HIV-1 Vpr Induces the Degradation of ZIP and sZIP, Adaptors of the NuRD Chromatin Remodeling Complex, by Hijacking DCAF1/VprBP

Maudet, Claire; Sourisce, Adèle; Dragin, Loïc; Lahouassa, Hichem; Rain, Jean-Christophe; Bouaziz, Serge; Ramirez, Bertha Cécilia; Margottin-Goguet, Florence

doi:10.1371/journal.pone.0077320

Cited by 27 publications

(23 citation statements)

References 64 publications

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“…Cell cycle arrest seems to involve Vpr association with the SLX4-SLX1-MUS81-EME1 complex, leading to SLX4 (Structure-specific endonuclease subunit) activation and ultimately proteasomal degradation of MUS81 (Crossover junction endonuclease) and EME1 (Essential Meiotic Structure-Specific Endonuclease 1) [ 127 , 128 ]. Vpr also induces the degradation of multiple other cellular proteins such as the DNA translocase HLTF (Helicase-Like Transcription Factor) [ 171 ], the DNA replication factor MCM10 (Mini Chromosome Maintenance 10) [ 172 ], as well as the chromatin associated proteins ZIP (leucine Zipper), sZIP and class I HDACs (Histone Deacetylase 6) [ 173 , 174 ].…”

Section: Other Cellular Proteins Targeted By the Hijacked Upsmentioning

confidence: 99%

Hijacking of the Ubiquitin/Proteasome Pathway by the HIV Auxiliary Proteins

Seissler

Marquet

Paillart

2017

Viruses

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The ubiquitin-proteasome system (UPS) ensures regulation of the protein pool in the cell by ubiquitination of proteins followed by their degradation by the proteasome. It plays a central role in the cell under normal physiological conditions as well as during viral infections. On the one hand, the UPS can be used by the cell to degrade viral proteins, thereby restricting the viral infection. On the other hand, it can also be subverted by the virus to its own advantage, notably to induce degradation of cellular restriction factors. This makes the UPS a central player in viral restriction and counter-restriction. In this respect, the human immunodeficiency viruses (HIV-1 and 2) represent excellent examples. Indeed, many steps of the HIV life cycle are restricted by cellular proteins, some of which are themselves components of the UPS. However, HIV itself hijacks the UPS to mediate defense against several cellular restriction factors. For example, the HIV auxiliary proteins Vif, Vpx and Vpu counteract specific restriction factors by the recruitment of cellular UPS components. In this review, we describe the interplay between HIV and the UPS to illustrate its role in the restriction of viral infections and its hijacking by viral proteins for counter-restriction.

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Section: Other Cellular Proteins Targeted By the Hijacked Upsmentioning

confidence: 99%

Hijacking of the Ubiquitin/Proteasome Pathway by the HIV Auxiliary Proteins

Seissler

Marquet

Paillart

2017

Viruses

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“…Host CRL4 complexes are required for the recognition of UV-DNA damage in the absence of viral infection [ 21 , 112 , 113 ], and indeed Vpr expression arrests cell cycle progression at the G2 phase, in a similar manner to a DNA-damage related checkpoint [ 114 ]. In recent years, several putative substrates of Vpr containing CRL4 complexes have been identified, [ 61 , 115 , 116 , 117 , 118 , 119 , 120 ] with uracil DNA glycosylases (UNG2 and SMUG1) being the first recognized [ 118 , 119 ]. Yet, the significance of these Vpr interactions in the context of cell cycle arrest or viral infection is not clear.…”

Section: How Do Viruses Affect Crls?mentioning

confidence: 99%

Cullin E3 Ligases and Their Rewiring by Viral Factors

et al. 2014

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The ability of viruses to subvert host pathways is central in disease pathogenesis. Over the past decade, a critical role for the Ubiquitin Proteasome System (UPS) in counteracting host immune factors during viral infection has emerged. This counteraction is commonly achieved by the expression of viral proteins capable of sequestering host ubiquitin E3 ligases and their regulators. In particular, many viruses hijack members of the Cullin-RING E3 Ligase (CRL) family. Viruses interact in many ways with CRLs in order to impact their ligase activity; one key recurring interaction involves re-directing CRL complexes to degrade host targets that are otherwise not degraded within host cells. Removal of host immune factors by this mechanism creates a more amenable cellular environment for viral propagation. To date, a small number of target host factors have been identified, many of which are degraded via a CRL-proteasome pathway. Substantial effort within the field is ongoing to uncover the identities of further host proteins targeted in this fashion and the underlying mechanisms driving their turnover by the UPS. Elucidation of these targets and mechanisms will provide appealing anti-viral therapeutic opportunities. This review is focused on the many methods used by viruses to perturb host CRLs, focusing on substrate sequestration and viral regulation of E3 activity.

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“…Some studies have suggested that Vpr is also an early viral protein because it is included in the infecting virion before de novo expression from proviral DNA (Maudet et al, 2013). Studies have shown that Vpr can induce neuronal apoptosis indirectly by stimulating the NFκB –mediated production of inflammatory cytokines (Guha et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Role of Neurotrophic Factor Alterations in the Neurodegenerative Process in HIV Associated Neurocognitive Disorders

Fields

Dumaop

Langford

et al. 2014

J Neuroimmune Pharmacol

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Migration of HIV infected cells into the CNS is associated with a spectrum of neurological disorders, ranging from milder forms of HIV-associated neurocognitive disorders (HAND) to HIV-associated dementia (HAD). These neuro-psychiatric syndromes are related to the neurodegenerative pathology triggered by the release of HIV proteins and cytokine/chemokines from monocytes/macrophages into the CNS –a condition known as HIV encephalitis (HIVE). As a result of more effective combined anti-retroviral therapy (cART) patients with HIV are living longer and thus the frequency of HAND has increased considerably, resulting in an overlap between the neurodegenerative pathology associated with HIV and that related to aging. In fact, HIV infection is believed to hasten the aging process. The mechanisms through which HIV and aging lead to neurodegeneration include: abnormal calcium flux, excitotoxicity, signaling abnormalities, oxidative stress and autophagy defects. Moreover, recent studies have shown that defects in the processing and transport of neurotrophic factors such as fibroblast growth factors (FGFs), neural growth factor (NGF) and brain-derived growth factor (BDNF) might also play a role. Recent evidence implicates alterations in neurotrophins in the pathogenesis of neurodegeneration associated with HAND in the context of aging. Here, we report FGF overexpression curtails gp120-induced neurotoxicity in a double transgenic mouse model. Furthermore, our data show disparities in brain neurotrophic factor levels may be exacerbated in HIV patients over 50 years of age. In this review, we discuss the most recent findings on neurotrophins and HAND in the context of developing new therapies to combat HIV infection in the aging population.

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HIV-1 Vpr Induces the Degradation of ZIP and sZIP, Adaptors of the NuRD Chromatin Remodeling Complex, by Hijacking DCAF1/VprBP

Cited by 27 publications

References 64 publications

Hijacking of the Ubiquitin/Proteasome Pathway by the HIV Auxiliary Proteins

Hijacking of the Ubiquitin/Proteasome Pathway by the HIV Auxiliary Proteins

Cullin E3 Ligases and Their Rewiring by Viral Factors

Role of Neurotrophic Factor Alterations in the Neurodegenerative Process in HIV Associated Neurocognitive Disorders

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