Viral manipulation of the cellular sumoylation machinery

Lowrey, Angela J.; Cramblet, Wyatt T.; Bentz, Gretchen L.

doi:10.1186/s12964-017-0183-0

Cited by 55 publications

(57 citation statements)

References 122 publications

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“…Viruses rely heavily on the host's cellular replication machinery, including the ability to by-pass and/or exploit cellular ubiquitin and SUMOylation conjugating systems, to successfully proliferate and achieve infection. Many viruses are able to target essentially every step of ubiquitination and SUMOylation processes, including the activation of genes that encode ubiquitin ligases or other molecules that alter the intracellular pools of free ubiquitin and SUMOs available for conjugation to proteins that modulate replication processes (42).…”

Section: Discussionmentioning

confidence: 99%

Transcriptional Profiling of Leukocytes in Critically Ill COVID19 Patients: Implications for Interferon Response and Coagulation

Gill

Santos

O’Gorman

et al. 2020

Preprint

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Background: COVID19 is caused by the SARS-CoV-2 virus and has been associated with severe inflammation leading to organ dysfunction and mortality. Our aim was to profile the transcriptome in leukocytes from critically ill patients positive for COVID19 compared to those negative for COVID19 to better understand the COVID19 associated host response. For these studies, all patients admitted to our tertiary care intensive care unit (ICU) suspected of being infected with SARS-CoV-2, using standardized hospital screening methodologies, had blood samples collected at the time of admission to the ICU. Transcriptome profiling of leukocytes via ribonucleic acid sequencing (RNAseq) was then performed and differentially expressed genes as well as significantly enriched gene sets were identified.Results: We enrolled seven COVID19+ (PCR positive, 2 SARS-CoV-2 genes) and seven age- and sex-matched COVID19- (PCR negative) control ICU patients. Cohorts were well-balanced with the exception that COVID19- patients had significantly higher total white blood cell counts and circulating neutrophils and COVID19+ patients were more likely to suffer bilateral pneumonia. The mortality rate for this cohort of COVID19+ ICU patients was 29%. Transcriptional analysis revealed that when compared to COVID19- patients, the altered transcriptional responses of leukocytes in critically ill COVID19+ ICU patients appeared to be associated with multiple interrelated outcomes, including but not limited to robust interferon (IFN)-associated transcriptional responses, a marked decrease in the transcriptional activity of genes contributing to protein synthesis and the dysregulated expression of genes that contribute to coagulation, platelet activation, Toll-like receptor activation, neurotrophin signalling, and protein SUMOylation/ubiquitination. Conclusions: Our findings demonstrate that critically ill COVID19+ patients on day 1 of admission to the ICU display a unique leukocyte transcriptional profile that distinguishes them from COVID19- patients, providing guidance for future targeted studies exploring novel prognostic and therapeutic aspects of COVID19.

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Section: Discussionmentioning

confidence: 99%

Transcriptional Profiling of Leukocytes in Critically Ill COVID19 Patients: Implications for Interferon Response and Coagulation

Gill

Santos

O’Gorman

et al. 2020

Preprint

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show abstract

“…Interestingly, oncogenic viral infections can also increase metabolic and proangiogenic markers through expression of a very specific domain that also controls SUMO enzymes expression (Pozzebon et al, 2013). Viral exploitation of SUMOylation has been recently detailed in elegant reviews Lowrey et al, 2017;Wilson, 2017), to which readers can refer. In the following sections we will provide some classic examples on how oncogenic viruses impact SUMOylation to increase their ability to infect, persist, and transform host cells.…”

Section: Sumo In Dna Damagementioning

confidence: 99%

Recent Highlights: Onco Viral Exploitation of the SUMO System

Mattoscio¹,

Medda²,

Chiocca³

2020

Current Issues in Molecular Biology

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Small ubiquitin-like modifier (SUMO)ylation is a crucial post-translational modification that controls functions of a wide collection of proteins and biological processes. Hence, given its pleiotropic role, viruses have developed many approaches to usurp SUMO conjugation to exploit the cellular host environment for their own benefit. Consistently, cancer cells also frequently impact on SUMO to force cellular transformation, underlining the importance of SUMO in health and diseases. Therefore, after a brief introduction to the multistep SUMOylation pathway, in this review we will focus our attention on several examples of strategies adopted by oncogenic viruses to hijack SUMOylation in order to promote infection, persistence and malignant transformation of host cells.caister.com/cimb Curr. Figure 3.1 The SUMO conjugation system. Ulp1/SENP proteases catalyse cleavage of the C-terminal domain of SUMO proteins, exposing a diglycine motif.Processed SUMO is transferred to a cysteine of the heterodimeric E1 enzyme Uba2/SAE1. SUMO is then conjugated to a cysteine of UBC9, the E2 enzyme and attached to a lysine residue of the consensus motif on target proteins. The conjugation is often facilitated by an E3-ligase, which enforces the interactions among the involved components. SUMOylation is a reversible pathway where the Ulp1/SENPs proteases dictate the de-SUMOylation process.caister.com/cimb 2 Curr. Issues Mol. Biol. Vol. 35Oncoviruses and SUMOylation | 37

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“…Viruses alter speci ic host cell targets, through various mechanisms, to counteract host defenses aimed at eliminating infectivity and viral propagation [366][367][368]. Post-translational modi ication (PTM) of proteins is important to numerous cellular events thus allowing cells to respond to both internal as well as external stimuli [367]. The most studied protein modi ications include: ubiquitination, phosphorylation, acetylation, methylation, and glycosylation [367].…”

Section: Sumo Proteins and Sumoylationmentioning

confidence: 99%

The beneficial effects of varicella zoster virus

Al-Anazi¹,

Wk²,

Al-Jasser³

2019

J Hematol Clin Res

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Varicella zoster virus behaves differently from other herpes viruses as it differs from them in many aspects. Recently, there has been growing evidence on the benefi cial effects of the virus in immune compromised hosts and these effects are translated into prolongation of survival. The reported benefi cial effects of the virus include: (1) stimulation of bone marrow activity in patients with hematologic malignancies and bone marrow failure syndromes, (2) antitumor effects in various hematologic malignancies and solid tumors, and (3) association with graft versus host disease which has anticancer effects. Additionally, there are several reports on the safety of the live-attenuated even in severely immune suppressed individuals and on the emerging role of the virus in cancer immunotherapy. In this review, the following aspects of the virus will be thoroughly discussed: (1) new data on the genetic background, pathogenesis, vaccination, and new therapeutic modalities; (2) bone marrow microenvironment and hematopoiesis; (3) cells involved in the pathogenesis of the virus such as: mesenchymal stem cells, dendritic cells, natural killer cells, T-cells and mononuclear cells; (4) cellular proteins such as open reading frames, glycoproteins, promyelocytic leukemia protein, chaperons, and SUMOs; (5) extracellular vesicles, exosomes, and micro-RNAs; and (6) signaling pathways, cytokines, and interferons.

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Viral manipulation of the cellular sumoylation machinery

Cited by 55 publications

References 122 publications

Transcriptional Profiling of Leukocytes in Critically Ill COVID19 Patients: Implications for Interferon Response and Coagulation

Transcriptional Profiling of Leukocytes in Critically Ill COVID19 Patients: Implications for Interferon Response and Coagulation

Recent Highlights: Onco Viral Exploitation of the SUMO System

The beneficial effects of varicella zoster virus

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