Impact of Adenovirus infection in host cell metabolism evaluated by 1H-NMR spectroscopy

Silva, Ana Carina; Teixeira, Ana Margarida; Alves, Paula M.

doi:10.1016/j.jbiotec.2016.05.025

Cited by 14 publications

(26 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many years passed between these initial observations and advances in high-throughput metabolomics technology that allowed for the first metabolomics study of virus-infected human cells in 2006 [30]. Indeed, thorough metabolomic studies of HAdV infected cells began in 2016 [31]. These metabolomic studies of HAdV infected cells will be discussed in the next section.…”

Section: The Earliest Observations Of Metabolic Changes Due To Hadmentioning

confidence: 99%

Metabolic Reprogramming of the Host Cell by Human Adenovirus Infection

Prusinkiewicz

Mymryk

2019

Viruses

View full text Add to dashboard Cite

Viruses are obligate intracellular parasites that alter many cellular processes to create an environment optimal for viral replication. Reprogramming of cellular metabolism is an important, yet underappreciated feature of many viral infections, as this ensures that the energy and substrates required for viral replication are available in abundance. Human adenovirus (HAdV), which is the focus of this review, is a small DNA tumor virus that reprograms cellular metabolism in a variety of ways. It is well known that HAdV infection increases glucose uptake and fermentation to lactate in a manner resembling the Warburg effect observed in many cancer cells. However, HAdV infection induces many other metabolic changes. In this review, we integrate the findings from a variety of proteomic and transcriptomic studies to understand the subtleties of metabolite and metabolic pathway control during HAdV infection. We review how the E4ORF1 protein of HAdV enacts some of these changes and summarize evidence for reprogramming of cellular metabolism by the viral E1A protein. Therapies targeting altered metabolism are emerging as cancer treatments, and similar targeting of aberrant components of virally reprogrammed metabolism could have clinical antiviral applications.

show abstract

Section: The Earliest Observations Of Metabolic Changes Due To Hadmentioning

confidence: 99%

Metabolic Reprogramming of the Host Cell by Human Adenovirus Infection

Prusinkiewicz

Mymryk

2019

Viruses

View full text Add to dashboard Cite

show abstract

“…Thus, the use of glutamine carbon is increased to support the TCA cycle, which is required for generation of other macromolecules, such as amino acids and lipids (2). The enhanced utilization of glutamine to replenish the TCA cycle is also reported in human cytomegalovirus infection (40) and adenovirus infection (41). An increase in the level of glutamine catabolism may reduce the level of this amino acid which is crucial for efficient function of immune cells (42).…”

Section: Discussionmentioning

confidence: 99%

Glutaminolysis and Glycolysis Are Essential for Optimal Replication of Marek’s Disease Virus

Boodhoo

Kamble

Sharif

et al. 2020

J Virol

View full text Add to dashboard Cite

Viruses may hijack glycolysis, glutaminolysis, or fatty acid β-oxidation of host cells to provide the energy and macromolecules required for efficient viral replication. Marek’s disease virus (MDV) causes a deadly lymphoproliferative disease in chickens and modulates metabolism of host cells. Metabolic analysis of MDV-infected chicken embryonic fibroblasts (CEFs) identified elevated levels of metabolites involved in glutamine catabolism, such as glutamic acid, alanine, glycine, pyrimidine, and creatine. In addition, our results demonstrate that glutamine uptake is elevated by MDV-infected cells in vitro. Although glutamine, but not glucose, deprivation significantly reduced cell viability in MDV-infected cells, both glutamine and glucose were required for virus replication and spread. In the presence of minimum glutamine requirements based on optimal cell viability, virus replication was partially rescued by the addition of the tricarboxylic acid (TCA) cycle intermediate, α-ketoglutarate, suggesting that exogenous glutamine is an essential carbon source for the TCA cycle to generate energy and macromolecules required for virus replication. Surprisingly, the inhibition of carnitine palmitoyltransferase 1a (CPT1a), which is elevated in MDV-infected cells, by chemical (etomoxir) or physiological (malonyl-CoA) inhibitors, did not reduce MDV replication, indicating that MDV replication does not require fatty acid β-oxidation. Taken together, our results demonstrate that MDV infection activates anaplerotic substrate from glucose to glutamine to provide energy and macromolecules required for MDV replication, and optimal MDV replication occurs when the cells do not depend on mitochondrial β-oxidation. IMPORTANCE Viruses can manipulate host cellular metabolism to provide energy and essential biosynthetic requirements for efficient replication. Marek’s disease virus (MDV), an avian alphaherpesvirus, causes a deadly lymphoma in chickens and hijacks host cell metabolism. This study provides evidence for the importance of glycolysis and glutaminolysis, but not fatty acid β-oxidation, as an essential energy source for the replication and spread of MDV. Moreover, it suggests that in MDV infection, as in many tumor cells, glutamine is used for generation of energetic and biosynthetic requirements of the MDV infection, while glucose is used biosynthetically.

show abstract

“…While most of the research regarding lipid metabolism and DNA virus infection has been performed within the herpesvirus arena, there are a number of reports of other DNA viruses usurping, or otherwise manipulating, host lipid metabolism. In a study comparing the metabolic phenotypes of two cell lines commonly used for the production of adenovirus vectors, Silva et al report substantial increases in glucose consumption and lactate secretion during the first 24 h post infection with Ad5 [84]. Additionally, infected cells exhibited increased choline consumption, suggesting an increase in phospholipid synthesis [84].…”

Section: Herpesvirusesmentioning

confidence: 99%

“…In a study comparing the metabolic phenotypes of two cell lines commonly used for the production of adenovirus vectors, Silva et al report substantial increases in glucose consumption and lactate secretion during the first 24 h post infection with Ad5 [84]. Additionally, infected cells exhibited increased choline consumption, suggesting an increase in phospholipid synthesis [84]. Changes in the utilization and production of other metabolites varied between cell lines and infection parameters.…”

Section: Herpesvirusesmentioning

confidence: 99%

Chewing the Fat: The Conserved Ability of DNA Viruses to Hijack Cellular Lipid Metabolism

Lange

Lagunoff

Tarakanova

2019

Viruses

View full text Add to dashboard Cite

Viruses manipulate numerous host factors and cellular pathways to facilitate the replication of viral genomes and the production of infectious progeny. One way in which viruses interact with cells is through the utilization and exploitation of the host lipid metabolism. While it is likely that most—if not all—viruses require lipids or intermediates of lipid synthesis to replicate, many viruses also actively induce lipid metabolic pathways to sustain a favorable replication environment. From the formation of membranous replication compartments, to the generation of ATP or protein modifications, viruses exhibit differing requirements for host lipids. Thus, while the exploitation of lipid metabolism is a common replication strategy, diverse viruses employ a plethora of mechanisms to co-opt these critical cellular pathways. Here, we review recent literature regarding the exploitation of host lipids and lipid metabolism specifically by DNA viruses. Importantly, furthering the understanding of the viral requirements for host lipids may offer new targets for antiviral therapeutics and provide opportunities to repurpose the numerous FDA-approved compounds targeting lipid metabolic pathways as antiviral agents.

show abstract

Impact of Adenovirus infection in host cell metabolism evaluated by 1H-NMR spectroscopy

Cited by 14 publications

References 58 publications

Metabolic Reprogramming of the Host Cell by Human Adenovirus Infection

Metabolic Reprogramming of the Host Cell by Human Adenovirus Infection

Glutaminolysis and Glycolysis Are Essential for Optimal Replication of Marek’s Disease Virus

Chewing the Fat: The Conserved Ability of DNA Viruses to Hijack Cellular Lipid Metabolism

Contact Info

Product

Resources

About