The antiviral enzyme viperin inhibits cholesterol biosynthesis

Grunkemeyer, Timothy J.; Ghosh, Soumi; Patel, Ayesha; Sajja, Keerthi; Windak, J.; Basrur, Venkatesha; Kim, Youngsoo; Nesvizhskii, Alexey I.; Kennedy, Robert T.; Marsh, E. Neil G.

doi:10.1016/j.jbc.2021.100824

Cited by 15 publications

(8 citation statements)

References 77 publications

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“…Such alternations interfere with the replication of several enveloped viruses, including of IAV, that particularly rely on the cellular membranes for virus entry, assembly, and release ( 35 , 36 ). Viperin also targets cholesterol and interferes with its biosynthesis and, consequently, with the replication of multiple enveloped viruses ( 37 ). In case of IAV infection, viperin inhibits the release of budding viral progeny from the host cell plasma membrane by interfering with lipid rafts formation ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

Human N-Alpha-Acetyltransferase 60 Promotes Influenza A Virus Infection by Dampening the Interferon Alpha Signaling

Ahmed

Husain

2022

Front. Immunol.

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N-alpha-acetyltransferase 60 (NAA60) is the most recently discovered N-terminal acetyltransferase and found only in multicellular eukaryotes. NAA60 localizes to the Golgi complex and is one of the only two N-terminal acetyltransferases known to localize to an organelle. Furthermore, NAA60 possesses a unique ability of catalyzing the acetylation of membrane-anchored proteins at the N-terminus and histones at the lysine side chains. Herein, we demonstrate that NAA60 exhibits proviral properties during influenza A virus (IAV) infection by interfering with the interferon (IFN) α signaling. We found that the depletion and overexpression of NAA60 reduced and enhanced, respectively, the IAV growth in a cell type- and IAV strain-independent manner. Mechanistically, the IAV-induced expression of IFNα was increased and decreased in NAA60-depleted and -overexpressing cells, respectively. Furthermore, the depletion of NAA60 enhanced the level of phosphorylated STAT1 transcription factor as well as the expression of several IFN-stimulated genes (ISGs) such as MX1, CH25H, IFITM3, ISG15 and viperin in infected cells. Whereas the overexpression of NAA60 produced opposite results. Finally, similar results were obtained when the NAA60-depleted cells were treated with purified IFNα. These findings, in conjunction with our recent findings where N-terminal acetylation of many host proteins increased in response to the IAV infection, indicate an important role of N-terminal acetylation during IAV replication.

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Section: Discussionmentioning

confidence: 99%

Human N-Alpha-Acetyltransferase 60 Promotes Influenza A Virus Infection by Dampening the Interferon Alpha Signaling

Ahmed

Husain

2022

Front. Immunol.

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“…Metabolic processes and their molecular signaling pathways have the effect on DC development and differentiation [ 17 ]. It is reported that Viperin could inhibit virus infection via reduced cholesterol biosynthesis or improve glucose metabolism [ 29 – 31 ]. However, in this study, Viperin did not influence cholesterol production or gene expression of important enzymes in the glycolytic pathway including SLC2α, PFKFB3, HK2, PDK1, HIF-1α and TKT (Supplementary Fig.…”

Section: Discussionmentioning

confidence: 99%

Viperin deficiency promotes dendritic cell activation and function via NF-kappaB activation during Mycobacterium tuberculosis infection

Zhou

et al. 2022

Inflamm. Res.

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Objectives and design Dendritic cells (DCs) are one of the key immune cells in bridging innate and adaptive immune response against Mycobacterium tuberculosis (Mtb) infection. Interferons (IFNs) play important roles in regulating DC activation and function. Virus-inhibitory protein, endoplasmic reticulum-associated, interferon-inducible (Viperin) is one of the important IFN-stimulated genes (ISGs), and elicits host defense against infection. Methods We investigated the effects and mechanisms of Viperin on DC activation and function using Viperin deficient bone marrow-derived dendritic cells (BMDCs) during Mtb infection. Results Viperin deficiency enhanced phagocytic activity and increased clearance of Mtb in DCs, produced higher abundance of NO, cytokine including interleukin-12 (IL-12), Tumor necrosis factor-α (TNF-α), IL-1β, IL-6 and chemokine including CXCL1, CXCL2 and CXCL10, elevated MHC I, MHC II and co-stimulatory molecules expression, and enhanced CD4+ and CD8+ T cell responses. Mechanistically, Viperin deficiency promoted DC activation and function through NF-κB p65 activation. NF-κB p65 inhibitor prevented cytokine and chemokine production, and co-stimulatory molecules expression promoted by Viperin deficiency. Conclusions These results suggest that Mtb induced Viperin expression could impair the activation of host defense function of DCs and DC-T cell cross talk during Mtb infection. This research may provide a potential target for future HDT in TB therapy.

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“…Indeed, many studies corroborate this proposal and demonstrate that human SAND has a role in modulating metabolism, regulating the activity/maturation of the immune cells, and inducing the expression of immune genes ( Figure 1B ). For example, the activity of SAND modulates central carbon metabolism ( Ebrahimi et al, 2020c ), regulates thermogenesis in adipose tissues ( Eom et al, 2019 ), inhibits thiolase activity of the trifunctional enzyme complex (a mitochondrial enzyme complex with three activities: enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and 3-ketoacyl-CoA thiolase) ( Dumbrepatil et al, 2020 ), and modulates cholesterol metabolism ( Tang et al, 2016 ; Grunkemeyer et al, 2021 ). It is required for optimal T helper two cell response ( Qiu et al, 2009 ) and chondrogenic differentiation via CXCL10 protein secretion ( Steinbusch et al, 2019 ).…”

Section: Main Textmentioning

confidence: 99%

Radical-SAM dependent nucleotide dehydratase (SAND), rectification of the names of an ancient iron-sulfur enzyme using NC-IUBMB recommendations

et al. 2022

Front. Mol. Biosci.

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Main textIn 1789, the influential French chemist Antoine-Laurent Lavoisier described his view of science and its langague in his book Traité élémentaire de chimie. According to the Robert Kerr's translation it states (Lavoisier, 1790): "As ideas are preserved and communicated by means of words, it necessarily follows that we cannot improve the language of any science without at the same time improving the science itself; neither can we, on the other hand, improve a science without improving the language or nomenclature which belongs to it." This view reminds us of Confucius's earlier doctrine, the rectification of names (Steinkraus, 1980;Lau, 2000). Confucius believed that rectification of names is imperative. He explained (Steinkraus, 1980;Lau, 2000): "If language is incorrect, then what is said does not concord with what was meant, what is to be done cannot be affected. If what is to be done cannot be affected, then rites and music will not flourish. If rites and music do not flourish, then mutilations and lesser punishments will go astray. And if mutilations and lesser punishments go astray, then the people have nowhere to put hand or foot. Therefore the gentleman uses only such language as is proper for speech, and only speaks of what it would be proper to carry into effect. The gentleman in what

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The antiviral enzyme viperin inhibits cholesterol biosynthesis

Cited by 15 publications

References 77 publications

Human N-Alpha-Acetyltransferase 60 Promotes Influenza A Virus Infection by Dampening the Interferon Alpha Signaling

Human N-Alpha-Acetyltransferase 60 Promotes Influenza A Virus Infection by Dampening the Interferon Alpha Signaling

Viperin deficiency promotes dendritic cell activation and function via NF-kappaB activation during Mycobacterium tuberculosis infection

Radical-SAM dependent nucleotide dehydratase (SAND), rectification of the names of an ancient iron-sulfur enzyme using NC-IUBMB recommendations

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