About: De novo Fatty Acid Biosynthesis Contributes Significantly to Establishment of a Bioenergetically Favorable Environment for Vaccinia Virus Infection

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About: De novo Fatty Acid Biosynthesis Contributes Significantly to Establishment of a Bioenergetically Favorable Environment for Vaccinia Virus Infection Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	De novo Fatty Acid Biosynthesis Contributes Significantly to Establishment of a Bioenergetically Favorable Environment for Vaccinia Virus Infection
Creator	Traktman, Paula Alwine, James Greseth, Matthew
Source	Medline; PMC
abstract	The poxvirus life cycle, although physically autonomous from the host nucleus, is nevertheless dependent upon cellular functions. A requirement for de novo fatty acid biosynthesis was implied by our previous demonstration that cerulenin, a fatty acid synthase inhibitor, impaired vaccinia virus production. Here we show that additional inhibitors of this pathway, TOFA and C75, reduce viral yield significantly, with partial rescue provided by exogenous palmitate, the pathway's end-product. Palmitate's major role during infection is not for phospholipid synthesis or protein palmitoylation. Instead, the mitochondrial import and β-oxidation of palmitate are essential, as shown by the impact of etomoxir and trimetazidine, which target these two processes respectively. Moreover, the impact of these inhibitors is exacerbated in the absence of exogenous glucose, which is otherwise dispensable for infection. In contrast to glucose, glutamine is essential for productive viral infection, providing intermediates that sustain the TCA cycle (anaplerosis). Cumulatively, these data suggest that productive infection requires the mitochondrial β-oxidation of palmitate which drives the TCA cycle and energy production. Additionally, infection causes a significant rise in the cellular oxygen consumption rate (ATP synthesis) that is ablated by etomoxir. The biochemical progression of the vaccinia life cycle is not impaired in the presence of TOFA, C75, or etomoxir, although the levels of viral DNA and proteins synthesized are somewhat diminished. However, by reversibly arresting infections at the onset of morphogenesis, and then monitoring virus production after release of the block, we determined that virion assembly is highly sensitive to TOFA and C75. Electron microscopic analysis of cells released into C75 revealed fragmented aggregates of viroplasm which failed to be enclosed by developing virion membranes. Taken together, these data indicate that vaccinia infection, and in particular virion assembly, relies on the synthesis and mitochondrial import of fatty acids, where their β-oxidation drives robust ATP production.
has issue date	2014-03-20(xsd:dateTime)
bibo:doi	10.1371/journal.ppat.1004021
bibo:pmid	24651651
has license	cc-by
sha1sum (hex)	dacb58b5ac7adedfeb44dde5632c503c5d37548f
schema:url	https://doi.org/10.1371/journal.ppat.1004021
resource representing a document's title	De novo Fatty Acid Biosynthesis Contributes Significantly to Establishment of a Bioenergetically Favorable Environment for Vaccinia Virus Infection
has PubMed Central identifier	PMC3961357
has PubMed identifier	24651651
schema:publication	PLoS Pathog
resource representing a document's body	covid:dacb58b5ac7adedfeb44dde5632c503c5d37548f#body_text
is schema:about of	named entity 'VACCINIA VIRUS INFECTION' named entity 'Infection' named entity 'productive' named entity 'demonstration' named entity 'viral' named entity 'cerulenin' named entity 'fatty acid' named entity 'essential' named entity 'highly' named entity 'Fatty' named entity 'Infection' named entity 'Establishment' named entity 'DIMINISHED' named entity 'VIRAL' named entity 'ONSET OF' named entity 'FUNCTIONS' named entity 'MITOCHONDRIAL' named entity 'PROTEIN PALMITOYLATION' named entity 'ABSENCE OF' named entity 'REDUCE' named entity 'C75' named entity 'FATTY ACID BIOSYNTHESIS' named entity 'DE NOVO' named entity 'TCA CYCLE' named entity 'RESCUE' named entity 'CONTRAST' named entity 'PROCESSES' named entity 'ESTABLISHMENT' named entity 'SOMEWHAT' named entity 'TARGET' named entity 'REQUIREMENT' named entity 'VIRION' named entity 'CELLS' named entity 'ESSENTIAL' named entity 'INFECTIONS' named entity 'PARTICULAR' named entity 'INHIBITORS' named entity 'IMPAIRED' named entity 'MONITORING' named entity 'INFECTION' named entity 'REVEALED' named entity '10%' named entity 'VIRUS PRODUCTION' named entity 'DETERMINED' named entity 'PHOSPHOLIPID SYNTHESIS' named entity 'THEIR' named entity 'THESE' named entity 'PRODUCTION' named entity 'VACCINIA VIRUS' named entity 'VIRAL DNA' named entity 'FAVORABLE' named entity 'VIRAL INFECTION' named entity 'OXYGEN CONSUMPTION RATE' named entity 'ENVIRONMENT' named entity 'EXACERBATED' named entity 'ANALYSIS' named entity 'WHERE' named entity 'ARRESTING' named entity 'PROVIDING' named entity 'ESTABLISHMENT' named entity 'DE NOVO' named entity 'ENVIRONMENT' named entity 'OUR' named entity 'EXOGENOUS' named entity 'ROLE' named entity 'MORPHOGENESIS' named entity 'PRESENCE OF' named entity 'NUCLEUS' named entity 'VACCINIA' named entity 'VIRION ASSEMBLY' named entity 'SYNTHESIS' named entity 'HIGHLY SENSITIVE' named entity 'SIGNIFICANT' named entity 'MEMBRANES' named entity 'CERULENIN' named entity 'TRIMETAZIDINE' named entity 'RELEASE' named entity 'LIFE CYCLE' named entity 'SUGGEST'

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