The Effects of Cytomegalovirus Infection on Polar Lipids and Neutral Lipids in Cultured Human Cells

Abrahamsen, L H; Clay, Melissa J.; Lyle, John; Zink, Jeffrey M.; Fredrikson, Lorna J.; DeSiervo, August J.; Jerkofsky, Maryann

doi:10.1159/000150521

Cited by 10 publications

(10 citation statements)

References 14 publications

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“…Virus infection alone resulted in a significant increase in intracellular cholesterol at 24 hpi. The increase is consistent with earlier work (Abrahamsen et al, 1996) and occurs in spite of the elevation of cell surface LRP1, which would favor its decrease.…”

Section: Resultssupporting

confidence: 92%

“…Since knockdown of LRP1 was shown previously to increase intracellular cholesterol levels (Zhou et al, 2009), cholesterol is important for replication of a variety of enveloped viruses (Pollock et al, 2010), and HCMV infection alters cholesterol levels (Abrahamsen et al, 1996), the cholesterol content of LRP1 knockdown cells was examined. As anticipated, when LRP1 activity was reduced by antibody or siRNA treatment, intracellular cholesterol levels assayed in extracts of cells lysed in buffer containing Triton X-100, increased at 24 h after mock or HCMV infection (Fig.…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Increased Expression of LDL Receptor-Related Protein 1 during Human Cytomegalovirus Infection Reduces Virion Cholesterol and Infectivity

Gudleski-O'Regan

Greco

Cristea

et al. 2012

Cell Host & Microbe

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Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Increased Expression of LDL Receptor-Related Protein 1 during Human Cytomegalovirus Infection Reduces Virion Cholesterol and Infectivity

Gudleski-O'Regan

Greco

Cristea

et al. 2012

Cell Host & Microbe

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“…This nuclear receptor is involved in the detoxification of xeno-and endobiotics, including cholesterolderived compounds (60). HCMV infection increases cholesterol synthesis (61) and intracellular cholesterol levels regulate the infectivity of progeny virus (62), so PXR may be required to prevent accumulation of toxic cholesterol byproducts.…”

Section: Discussionmentioning

confidence: 99%

Estrogen-related receptor α is required for efficient human cytomegalovirus replication

Hwang¹,

Purdy

Wu³

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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An shRNA-mediated screen of the 48 human nuclear receptor genes identified multiple candidates likely to influence the production of human cytomegalovirus in cultured human fibroblasts, including the estrogen-related receptor α (ERRα), an orphan nuclear receptor. The 50-kDa receptor and a 76-kDa variant were induced posttranscriptionally following infection. Genetic and pharmacological suppression of the receptor reduced viral RNA, protein, and DNA accumulation, as well as the yield of infectious progeny. In addition, RNAs encoding multiple metabolic enzymes, including enzymes sponsoring glycolysis (enolase 1, triosephosphate isomerase 1, and hexokinase 2), were reduced when the function of ERRα was inhibited in infected cells. Consistent with the effect on RNAs, a substantial number of metabolites, which are normally induced by infection, were either not increased or were increased to a reduced extent in the absence of normal ERRα activity. We conclude that ERRα is needed for the efficient production of cytomegalovirus progeny, and we propose that the nuclear receptor contributes importantly to the induction of a metabolic environment that supports optimal cytomegalovirus replication.herpesvirus | metabolism | nuclear receptor | mass spectrometry H uman cytomegalovirus (HCMV) belongs to the β-herpesvirus subfamily, and although most healthy individuals remain asymptomatic subsequent to infection, the pathogen is a major contributor to birth defects and to life-threatening disease in immunocompromised patients (1-3). As with all viruses, HCMV depends on the host cell to provide macromolecular building blocks for virion production, and throughout the course of its evolution, HCMV has adapted to manipulate numerous fundamental cellular processes, including RNA accumulation (4), translation (5), metabolism (6, 7), secretory pathways (8), and the cell cycle (9).The nuclear receptor gene family, of which there are 48 members in the human genome, encodes transcription factors (10). Some bind to specific hydrophobic ligands such as steroids, vitamin D, fatty acids, and lipids, providing a means to sense changes in the extracellular or intracellular environment; others are "orphans" with no known ligand, and are often constitutively active (11). As transcription factors that modulate broad gene regulatory networks, nuclear receptors control numerous physiological processes, including aspects of metabolism (cell autonomously and at the whole-organism level), development, and cellular differentiation, cancer, circadian rhythm, and immunity (11).The first indication that nuclear receptor signaling modulates HCMV replication surfaced after the identification of a retinoic acid response element within the major immediate-early promoter (MIEP) that caused a dose-dependent response to retinoic acid in reporter assays (12). Retinoic acid was further shown to enhance viral DNA replication and progeny production in human embryonal carcinoma cells and foreskin fibroblasts (13,14). The ligand also exacerbated symptoms of infection,...

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“…In addition to promoting fatty acid synthesis, HCMV has also been demonstrated to modify cholesterol synthesis [65] and trafficking [42,66]. HCMV infection has been proposed to increase cholesterol efflux through two recently reported mechanisms.…”

Section: Herpesvirusesmentioning

confidence: 99%

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

Lange

Lagunoff

Tarakanova

2019

Viruses

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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.

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The Effects of Cytomegalovirus Infection on Polar Lipids and Neutral Lipids in Cultured Human Cells

Cited by 10 publications

References 14 publications

Increased Expression of LDL Receptor-Related Protein 1 during Human Cytomegalovirus Infection Reduces Virion Cholesterol and Infectivity

Increased Expression of LDL Receptor-Related Protein 1 during Human Cytomegalovirus Infection Reduces Virion Cholesterol and Infectivity

Estrogen-related receptor α is required for efficient human cytomegalovirus replication

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

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