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

Seissler, Tanja; Marquet, Roland; Paillart, Jean-Christophe

doi:10.3390/v9110322

Cited by 59 publications

(48 citation statements)

References 175 publications

(233 reference statements)

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“…Among these viruses, some encode specific proteins that modify the host Ub machinery. For example, human immunodeficiency virus auxiliary protein, Vif, Vpx, and Vpu can hijack the UPS to facilitate viral propagation in host cells [54]. Some viruses even encode their own ubiquitinating or deubiquitinating enzymes (DUB), and a total of 28 viruse-encoded DUBs including herpesviral DUBs were summarized by Bailey-Elkin et al [55].…”

Section: Viruses Manipulate the Ups To Favour Viral Propagationmentioning

confidence: 99%

“…In this respect, the human immunodeficiency viruses (HIV-1 and 2) represent excellent examples. For example, the HIV accessory proteins Vif, Vpx and Vpu can hijack the UPS to exert their counter defence [54]. Some viruses can recruit cellular E3 ligases to target anti-viral proteins for degradation.…”

Section: Degradation Of Cellular Proteins By the Ups During Viral Infmentioning

confidence: 99%

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Pleiotropic roles of the ubiquitin-proteasome system during viral propagation

Tang

Chen

et al. 2018

Life Sciences

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Protein ubiquitination is a highly conserved post-translational modification affecting various biological processes including viral propagation. Ubiquitination has multiple effects on viral propagation, including viral genome uncoating, viral replication, and immune evasion. Ubiquitination of viral proteins is triggered by the ubiquitin-proteasome system (UPS). This involves the covalent attachment of the highly conserved 76 amino acid residue ubiquitin protein to target proteins by the consecutive actions of E1, E2 and E3 enzymes, and the 26S proteasome that together form a multiprotein complex that degrades target proteins. The UPS is the primary cytosolic proteolytic machinery for the selective degradation of various forms of proteins including viral proteins, thereby limiting viral growth in host cells. To combat this host anti-viral machinery, viruses have evolved the ability to employ or subvert the UPS to inactivate or degrade cellular proteins to favour viral propagation. This review highlights our current knowledge on the different roles of the UPS during viral propagation.

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Section: Viruses Manipulate the Ups To Favour Viral Propagationmentioning

confidence: 99%

Section: Degradation Of Cellular Proteins By the Ups During Viral Infmentioning

confidence: 99%

Pleiotropic roles of the ubiquitin-proteasome system during viral propagation

Tang

Chen

et al. 2018

Life Sciences

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“…Although humans are equipped with a variety of intrinsic, innate, and adaptive antiviral immune responses, HIV-1 has evolved sophisticated evasion strategies to specifically counteract the cellular antiviral defense [92,93]. Once activated, sensing pathways ultimately result in increased expression of host restriction factors.…”

Section: Counteraction Of Hiv-1 Restriction Factorsmentioning

confidence: 99%

Sensor Sensibility—HIV-1 and the Innate Immune Response

Yin

Langer

Zhang

et al. 2020

Cells

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Innate immunity represents the human immune system’s first line of defense against a pathogenic intruder and is initiated by the recognition of conserved molecular structures known as pathogen-associated molecular patterns (PAMPs) by specialized cellular sensors, called pattern recognition receptors (PRRs). Human immunodeficiency virus type 1 (HIV-1) is a unique human RNA virus that causes acquired immunodeficiency syndrome (AIDS) in infected individuals. During the replication cycle, HIV-1 undergoes reverse transcription of its RNA genome and integrates the resulting DNA into the human genome. Subsequently, transcription of the integrated provirus results in production of new virions and spreading infection of the virus. Throughout the viral replication cycle, numerous nucleic acid derived PAMPs can be recognized by a diverse set of innate immune sensors in infected cells. However, HIV-1 has evolved efficient strategies to evade or counteract this immune surveillance and the downstream responses. Understanding the molecular underpinnings of the concerted actions of the innate immune system, as well as the corresponding viral evasion mechanisms during infection, is critical to understanding HIV-1 transmission and pathogenesis, and may provide important guidance for the design of appropriate adjuvant and vaccine strategies. Here, we summarize current knowledge of the molecular basis for sensing HIV-1 in human cells, including CD4+ T cells, dendritic cells, and macrophages. Furthermore, we discuss the underlying mechanisms by which innate sensing is regulated, and describe the strategies developed by HIV-1 to evade sensing and immune responses.

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“…The ubiquitin‐proteasome system ensures regulation of the protein pool in eukaryotic cells by ubiquitination and proteasome‐mediated degradation. It plays an important role in a variety of basic cellular processes as well as many viral infections . Ubiquitination involves at least three classes of enzymes: ubiquitin‐activating enzymes, ubiquitin‐conjugating enzymes (E2s), and ubiquitin‐protein ligases .…”

mentioning

confidence: 99%

A Functional Variant in Ubiquitin Conjugating Enzyme E2 L3 Contributes to Hepatitis B Virus Infection and Maintains Covalently Closed Circular DNA Stability by Inducing Degradation of Apolipoprotein B mRNA Editing Enzyme Catalytic Subunit 3A

et al. 2019

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Hepatitis B virus (HBV) infection is a common infectious disease, in which nuclear covalently closed circular DNA(cccDNA) plays a key role in viral persistence, viral reactivation after treatment withdrawal, and drug resistance. A recent genome-wide association study has identified that the ubiquitin conjugating enzyme E2 L3 (UBE2L3) gene is associated with increased susceptibility to chronic HBV (CHB) infection in adults. However, the association between UBE2L3 and children with CHB and the underlying mechanism remain unclear. In this study, we performed two-stage case-control studies including adults and independent children in the Chinese Han population. The rs59391722 allele in the promoter of the UBE2L3 gene was significantly associated with HBV infection in both adults and children, and it increased the promoter activity of UBE2L3. Serum UBE2L3 protein levels were positively correlated with HBV viral load and hepatitis B e antigen (HBeAg) levels in children with CHB. In an HBV infection cell model, UBE2L3 knockdown significantly reduced total HBV RNAs, 3.5-kb RNA, as well as cccDNA in HBV-infected HepG2-Na + /taurocholate cotransporting polypeptide cells and human primary hepatocytes. A mechanistic study found that UBE2L3 maintained cccDNA stability by inducing proteasome-dependent degradation of apolipoprotein B mRNA editing enzyme catalytic subunit 3A, which is responsible for the degradation of HBV cccDNA. Moreover, interferon-α (IFN-α) treatment markedly decreased UBE2L3 expression, while UBE2L3 silencing reinforced the antiviral activity of IFN-α on HBV RNAs, cccDNA, and DNA. rs59391722 in UBE2L3 was correlated with HBV DNA suppression and HBeAg loss in response to IFN-α treatment of children with CHB. Conclusion: These findings highlight a host gene, UBE2L3, contributing to the susceptibility to persistent HBV infection; UBE2L3 may be involved in IFN-mediated viral suppression and serve as a potential target in the prevention and treatment of HBV infection. (Hepatology 2019;69:1885-1902). H epatitis B virus (HBV) infection is a worldwide health problem that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma. (1,2) Recent studies estimated that the global prevalence of HBV surface antigen (HBsAg) in 2016 was 3.9%, with 291 million individuals with HBV infection. (3)

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

Cited by 59 publications

References 175 publications

Pleiotropic roles of the ubiquitin-proteasome system during viral propagation

Pleiotropic roles of the ubiquitin-proteasome system during viral propagation

Sensor Sensibility—HIV-1 and the Innate Immune Response

A Functional Variant in Ubiquitin Conjugating Enzyme E2 L3 Contributes to Hepatitis B Virus Infection and Maintains Covalently Closed Circular DNA Stability by Inducing Degradation of Apolipoprotein B mRNA Editing Enzyme Catalytic Subunit 3A

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