Targeted induction of<i>de novo</i>Fatty acid synthesis enhances MDV replication in a COX-2/PGE<sub>2α</sub>dependent mechanism through EP2 and EP4 receptors engagement

Boodhoo, Nitish; Kamble, Nitin Machindra; Kaufer, Benedikt B.; Behboudi, Shahriar

doi:10.1101/323840

Cited by 4 publications

(1 citation statement)

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“…In this process, acetyl‐CoA is converted to malonyl‐CoA by ACC and subsequently to palmitate. Palmitic acid has several roles in biological functions such as fatty acid oxidation, β‐oxidation in the mitochondria, posttranslational modification (palmitoylation) of proteins, or elongation of fatty acid chains to energy production 147,148 . Assembly of VACA in VACV‐infected cells is reduced following the inhibition of fatty acid synthase by C75, an inhibitor of fatty acid synthase, and 5‐(tetradecyloxy)‐2‐furoic acid, an inhibitor of ACC 116 …”

Section: Poxviridaementioning

confidence: 99%

Interplay between cellular metabolism and DNA viruses

Zandi¹,

Shokri

Mahmoudvand

et al. 2022

Journal of Medical Virology

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Viruses as intracellular pathogens take over the host metabolism and reprogram to facilitate optimal virus production. DNA viruses can cause alterations in several metabolic pathways, including aerobic glycolysis also known as the Warburg effect, pentose phosphate pathway activation, and amino acid catabolism such as glutaminolysis, nucleotide biosynthesis, lipid metabolism, and amino acid biosynthesis. The available energy for productive infection can be increased in infected cells via modification of different carbon source utilization. This review discusses the metabolic alterations of the DNA viruses that will be the basis for future novel therapeutic approaches.

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Section: Poxviridaementioning

confidence: 99%

Interplay between cellular metabolism and DNA viruses

Zandi¹,

Shokri

Mahmoudvand

et al. 2022

Journal of Medical Virology

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Replication of Marek's Disease Virus Is Dependent on Synthesis of De Novo Fatty Acid and Prostaglandin E ₂

Boodhoo

Kamble

Kaufer

et al. 2019

J Virol

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Marek’s disease virus (MDV) causes deadly lymphoma and induces an imbalance of the lipid metabolism in infected chickens. Here, we discovered that MDV activates the fatty acid synthesis (FAS) pathway in primary chicken embryo fibroblasts (CEFs). In addition, MDV-infected cells contained high levels of fatty acids and showed increased numbers of lipid droplets (LDs). Chemical inhibitors of the FAS pathway (TOFA and C75) reduced MDV titers by approximately 30-fold. Addition of the downstream metabolites, including malonyl-coenzyme A and palmitic acid, completely restored the inhibitory effects of the FAS inhibitors. Furthermore, we could demonstrate that MDV infection activates the COX-2/prostaglandin E2 (PGE2) pathway, as evident by increased levels of arachidonic acid, COX-2 expression, and PGE2 synthesis. Inhibition of the COX-2/PGE2 pathway by chemical inhibitors or knockdown of COX2 using short hairpin RNA reduced MDV titers, suggesting that COX-2 promotes virus replication. Exogenous PGE2 completely restored the inhibition of the COX-2/PGE2 pathway in MDV replication. Unexpectedly, exogenous PGE2 also partially rescued the inhibitory effects of FAS inhibitors on MDV replication, suggesting that there is a link between these two pathways in MDV infection. Taken together, our data demonstrate that the FAS and COX-2/PGE2 pathways play an important role in the replication of this deadly pathogen. IMPORTANCE Disturbances of the lipid metabolism in chickens infected with MDV contribute to the pathogenesis of disease. However, the role of lipid metabolism in MDV replication remained unknown. Here, we demonstrate that MDV infection activates FAS and induces LD formation. Moreover, our results demonstrate that MDV replication is highly dependent on the FAS pathway and the downstream metabolites. Finally, our results reveal that MDV also activates the COX-2/PGE2 pathway, which supports MDV replication by activating PGE2/EP2 and PGE2/EP4 signaling pathways.

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Virus Infections and Host Metabolism—Can We Manage the Interactions?

et al. 2021

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When viruses infect cells, they almost invariably cause metabolic changes in the infected cell as well as in several host cell types that react to the infection. Such metabolic changes provide potential targets for therapeutic approaches that could reduce the impact of infection. Several examples are discussed in this review, which include effects on energy metabolism, glutaminolysis and fatty acid metabolism. The response of the immune system also involves metabolic changes and manipulating these may change the outcome of infection. This could include changing the status of herpesviruses infections from productive to latency. The consequences of viral infections which include coronavirus disease 2019 (COVID-19), may also differ in patients with metabolic problems, such as diabetes mellitus (DM), obesity, and endocrine diseases. Nutrition status may also affect the pattern of events following viral infection and examples that impact on the pattern of human and experimental animal viral diseases and the mechanisms involved are discussed. Finally, we discuss the so far few published reports that have manipulated metabolic events in-vivo to change the outcome of virus infection. The topic is expected to expand in relevance as an approach used alone or in combination with other therapies to shape the nature of virus induced diseases.

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Targeted induction ofde novoFatty acid synthesis enhances MDV replication in a COX-2/PGE_2αdependent mechanism through EP2 and EP4 receptors engagement

Cited by 4 publications

References 50 publications

Interplay between cellular metabolism and DNA viruses

Interplay between cellular metabolism and DNA viruses

Replication of Marek's Disease Virus Is Dependent on Synthesis of De Novo Fatty Acid and Prostaglandin E ₂

Virus Infections and Host Metabolism—Can We Manage the Interactions?

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Targeted induction ofde novoFatty acid synthesis enhances MDV replication in a COX-2/PGE2αdependent mechanism through EP2 and EP4 receptors engagement

Cited by 4 publications

References 50 publications

Interplay between cellular metabolism and DNA viruses

Interplay between cellular metabolism and DNA viruses

Replication of Marek's Disease Virus Is Dependent on Synthesis of De Novo Fatty Acid and Prostaglandin E 2

Virus Infections and Host Metabolism—Can We Manage the Interactions?

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Targeted induction ofde novoFatty acid synthesis enhances MDV replication in a COX-2/PGE_2αdependent mechanism through EP2 and EP4 receptors engagement

Replication of Marek's Disease Virus Is Dependent on Synthesis of De Novo Fatty Acid and Prostaglandin E ₂