Viperin Reveals Its True Function

Rivera-Serrano, Efraín E.; Gizzi, Anthony S.; Arnold, Jamie J.; Grove, Tyler L.; Almo, Steven C.; Cameron, Craig Ε.

doi:10.1146/annurev-virology-011720-095930

Cited by 92 publications

(85 citation statements)

References 105 publications

(176 reference statements)

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“…Notably, the ubiquitin-like protein ISG15 exerts its antiviral function intracellularly by ISGylation of viral proteins and also extracellularly by acting in a cytokine-like manner to promote IFN-γ production of NK cells and T cells (59). Viperin ( RSAD2 ), a multifunctional antiviral factor (60) has recently gained attention, as it was shown to act as a synthase for antiviral ribonucleotides (61).…”

Section: Resultsmentioning

confidence: 99%

Transcriptomic signature and metabolic programming of bovine classical and nonclassical monocytes indicate distinct functional specializations

Talker

Barut

Rufener

et al. 2020

Preprint

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Similar to human monocytes, bovine monocytes can be split into CD14+CD16- classical and CD14-CD16+ nonclassical monocytes (cM and ncM, respectively). Here, we present an in-depth analysis of their steady-state transcriptomes, highlighting pronounced functional specializations. Gene transcription indicates that pro-inflammatory and antibacterial processes are associated with cM, while ncM appear to be specialized in regulatory/anti-inflammatory functions and tissue repair, as well as antiviral responses and T-cell immunomodulation. In support of these functional differences, we found that oxidative phosphorylation prevails in ncM, whereas cM are clearly biased towards aerobic glycolysis. Furthermore, bovine monocyte subsets differed in their responsiveness to TLR ligands, supporting an antiviral role of ncM. Taken together, these data clearly indicate a variety of subset-specific functions in cM and ncM that are likely to be transferable to monocyte subsets of other species, including humans.

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Section: Resultsmentioning

confidence: 99%

Transcriptomic signature and metabolic programming of bovine classical and nonclassical monocytes indicate distinct functional specializations

Talker

Barut

Rufener

et al. 2020

Preprint

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“…In a more traditional application analogous to its use in the field of drug discovery, molecular docking has also been used to evaluate proposed substrates of the rSAM enzyme viperin (virus inhibitory protein, endoplasmic reticulum-associated, interferon-inducible; Table 1 ). Viperin orthologs are ubiquitous across all domains of life, including in humans, and have been demonstrated to inhibit viral replication [ 24 , 25 ]. The molecular mechanism underlying this antiviral activity, however, was only recently determined [ 26 ].…”

Section: Molecular Dockingmentioning

confidence: 99%

Computational Approaches: An Underutilized Tool in the Quest to Elucidate Radical SAM Dynamics

Davis¹

2021

Molecules

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Enzymes are biological catalysts whose dynamics enable their reactivity. Visualizing conformational changes, in particular, is technically challenging, and little is known about these crucial atomic motions. This is especially problematic for understanding the functional diversity associated with the radical S-adenosyl-L-methionine (SAM) superfamily whose members share a common radical mechanism but ultimately catalyze a broad range of challenging reactions. Computational chemistry approaches provide a readily accessible alternative to exploring the time-resolved behavior of these enzymes that is not limited by experimental logistics. Here, we review the application of molecular docking, molecular dynamics, and density functional theory, as well as hybrid quantum mechanics/molecular mechanics methods to the study of these enzymes, with a focus on understanding the mechanistic dynamics associated with turnover.

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“…3 / Further stressing the importance of CTP, during evolution, innate antiviral immunity recruited the activity of an enzyme, viperin, which modifies CTP into a form toxic to the development of the virus, 3ʹ-deoxy-3′,4ʹ-didehydro-CTP (ddhCTP) [20]. An interesting consequence of this pathway is that decreasing the C content of the genome will allow the virus replication process to be less sensitive to the presence of this nucleobase.…”

Section: Description and Analysis Of The Evolution Of The C Content Omentioning

confidence: 99%

Biochemical and mathematical lessons from the evolution of the SARS-CoV-2 virus: paths for novel antiviral warfare

Cluzel¹,

Lambert

Maday³

et al. 2020

Preprint

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In the fight against the spread of COVID-19 the emphasis is on vaccination or on reactivating existing drugs used for other purposes. The tight links that necessarily exist between the virus as it multiplies and the metabolism of its host are systematically ignored. Here we show that the metabolism of all cells is coordinated by the availability of a core building block of the cell’s genome, cytidine triphosphate (CTP). This metabolite is also the key to the synthesis of the viral envelope and to the translation of its genome into proteins. This unique role explains why evolution has led to the early emergence in animals of an antiviral immunity enzyme, viperin, that synthesizes a toxic analogue of CTP. The constraints arising from this dependency guide the evolution of the virus. With this in mind, we explored the real-time experiment taking place before our eyes using probabilistic modelling approaches to the molecular evolution of the virus. We have thus followed, almost on a daily basis, the evolution of the composition of the viral genome to link it to the progeny produced over time, particularly in the form of blooms that sparked a firework of viral mutations. Some of those certainly increase the propagation of the virus. This led us to make out the critical role in this evolution of several proteins of the virus, such as its nucleocapsid N, and more generally to begin to understand how the virus ties up the host metabolism to its own benefit. A way for the virus to escape CTP-dependent control in cells would be to infect cells that are not expected to grow, such as neurons. This may account for unexpected body sites of viral development in the present epidemic.

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Viperin Reveals Its True Function

Cited by 92 publications

References 105 publications

Transcriptomic signature and metabolic programming of bovine classical and nonclassical monocytes indicate distinct functional specializations

Transcriptomic signature and metabolic programming of bovine classical and nonclassical monocytes indicate distinct functional specializations

Computational Approaches: An Underutilized Tool in the Quest to Elucidate Radical SAM Dynamics

Biochemical and mathematical lessons from the evolution of the SARS-CoV-2 virus: paths for novel antiviral warfare

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