The Deubiquitinase USP29 Promotes SARS-CoV-2 Virulence by Preventing Proteasome Degradation of ORF9b

Gao, Wenying; Wang, Liuli; Ju, Xiaohui; Zhao, Simin; Li, Zhaolong; Su, Manman; Xu, Jiancheng; Wang, Pei‐Hui; Ding, Qiang; Lv, Guoyue; Zhang, Wenyan

doi:10.1128/mbio.01300-22

Cited by 16 publications

(9 citation statements)

References 27 publications

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“…Furthermore, one of the dominant pathogenic properties of MERS is its ability to inhibit the host bronchial interferon synthesis [48] . Likewise, experimental studies showed that SARS-CoV-2 poorly stimulates the IFN-I response, which is crucial in the combat against viruses [49] .…”

Section: Resultsmentioning

confidence: 99%

The favorable impacts of silibinin polyphenols as adjunctive therapy in reducing the complications of COVID-19: A review of research evidence and underlying mechanisms

Musazadeh

Karimi²,

bagheri³

et al. 2022

Biomedicine & Pharmacotherapy

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Section: Resultsmentioning

confidence: 99%

The favorable impacts of silibinin polyphenols as adjunctive therapy in reducing the complications of COVID-19: A review of research evidence and underlying mechanisms

Musazadeh

Karimi²,

bagheri³

et al. 2022

Biomedicine & Pharmacotherapy

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“…Ubiquitination signaling is crucial for immunity to limit the spread of pathogens, thus, it plays a critical role in the viral pathogenicity of SARS-CoV-2. For example, aberrant USP29 deubiquitylation could enhance the virulence of SARS-CoV-2 by preventing proteasome degradation of ORF9b ( 34 ). One of the underlying mechanisms why SARS-CoV-2 infection can promote autoinflammatory disease was that SARS-CoV-2 affects UBA1 and ubiquitination in an inappropriate way ( 35 ).…”

Section: Discussionmentioning

confidence: 99%

Exploration of the common genetic landscape of COVID-19 and male infertility

et al. 2023

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BackgroundCOVID-19 has spread widely across continents since 2019, causing serious damage to human health. Accumulative research uncovered that SARS-CoV-2 poses a great threat to male fertility, and male infertility (MI) is a common comorbidity for the COVID-19 pandemic. The aim of the study was to explore the cross-talk molecular mechanisms between COVID-19 and MI.Materials and methodsA total of four transcriptome data regarding COVID-19 and MI were downloaded from the Gene Expression Omnibus (GEO) repository, and were divided for two purposes (initial analysis and external validation). Differentially expressed genes (DEGs) analysis, GO and pathway annotation, protein-protein interaction (PPI) network, connectivity ranking, ROC analysis, immune infiltration, and translational and post-translational interaction were performed to gain hub COVID-19-related DEGs (CORGs). Moreover, we recorded medical information of COVID-19 patients with MI and matched healthy controls, and harvested their sperm samples in the university hospital. Expressions of hub CORGs were detected through the qRT-PCR technique.ResultsWe identified 460 overlapped CORGs in both the COVID-19 DEGs and MI DEGs. CORGs were significantly enriched in DNA damage and repair-associated, cell cycle-associated, ubiquitination-associated, and coronavirus-associated signaling. Module assessment of PPI network revealed that enriched GO functions were closely related to cell cycle and DNA metabolism processes. Pharmacologic agent prediction displayed protein-drug interactions of ascorbic acid, biotin, caffeine, and L-cysteine with CORGs. After connectivity ranking and external validation, three hub CORGs (ENTPD6, CIB1, and EIF3B) showed good diagnostic performance (area under the curve > 0.75). Subsequently, three types of immune cells (CD8+ T cells, monocytes, and macrophages M0) were dominantly enriched, and 24 transcription factor-CORGs interactions and 13 miRNA-CORGs interactions were constructed in the network. Finally, qRT-PCR analysis confirmed that there were significant differences in the expression of hub CORGs (CIB1 and EIF3B) between the patient and control groups.ConclusionThe present study identified and validated hub CORGs in COVID-19 and MI, and systematically explored molecular interactions and regulatory features in various biological processes. Our data provide new insights into the novel biomarkers and potential therapeutic targets of COVID-19-associated MI.

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“…Eleven SARS‐CoV‐2 proteins contain 135 ubiquitin residues, from at least 1 ubiquitination residue to 66 residues of a single protein 35 . It has been reported that the deubiquitinase USP29 promotes SARS‐CoV‐2 virulence by preventing proteasome degradation of ORF9b 36 . Strikingly, compared to the lower ubiquitination expression in other tissues, the lymphatic tissue possessed activated ubiquitination, probably relating to the host immune response against SARS‐CoV‐2.…”

Section: Discussionmentioning

confidence: 99%

Elevated ubiquitination contributes to protective immunity against severe SARS‐CoV‐2 infection

Che

Jiang

Zhang

et al. 2022

Clinical & Translational Med

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Background The crosstalk between the ubiquitin‐proteasome and the immune system plays an important role in the health and pathogenesis of viral infection. However, there have been few studies of ubiquitin activation in severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. Methods We investigated the effect of ubiquitination on SARS‐CoV‐2 infection and patient prognosis by integrating published coronavirus disease 2019 (COVID‐19) multi‐transcriptome data and bioinformatics methods. Results The differential expression of COVID‐19 samples revealed changed ubiquitination in most solid and hollow organs, and it was activated in lymphatic and other immune tissues. In addition, in the respiratory system of COVID‐19 patients, the immune response was mainly focused on the alveoli, and the expression of ubiquitination reflected increasing immune infiltration. Ubiquitination stratification could significantly differentiate patients' prognosis and inflammation levels through the general transcriptional analysis of the peripheral blood of patients with COVID‐19. Moreover, high ubiquitination levels were associated with a favourable prognosis, low inflammatory response, and reduced mechanical ventilation and intensive care unit. Moreover, high ubiquitination promoted a beneficial immune response while inhibiting immune damage. Finally, prognostic stratification and biomarker screening based on ubiquitination traits played an important role in clinical management and drug development. Conclusion Ubiquitination characteristics provides new ideas for clinical intervention and prognostic guidance for COVID‐19 patients.

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The Deubiquitinase USP29 Promotes SARS-CoV-2 Virulence by Preventing Proteasome Degradation of ORF9b

Abstract: Coronavirus disease 2019 (COVID-19) is a current global health threat caused by SARS-CoV-2. The innate immune response such as type I IFN (IFN-I) is the first line of host defense against viral infections, whereas SARS-CoV-2 proteins antagonize IFN-I production through distinct mechanisms.

Cited by 16 publications

References 27 publications

The favorable impacts of silibinin polyphenols as adjunctive therapy in reducing the complications of COVID-19: A review of research evidence and underlying mechanisms

The favorable impacts of silibinin polyphenols as adjunctive therapy in reducing the complications of COVID-19: A review of research evidence and underlying mechanisms

Exploration of the common genetic landscape of COVID-19 and male infertility

Elevated ubiquitination contributes to protective immunity against severe SARS‐CoV‐2 infection

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