Evidence map›Paper›PMID 25122799›Full record

ArticleJournal of virology2014

The composition of West Nile virus lipid envelope unveils a role of sphingolipid metabolism in flavivirus biogenesis.

Miguel A Martín-Acebes, Teresa Merino-Ramos, Ana-Belén Blázquez, Josefina Casas, Estela Escribano-Romero, Francisco Sobrino, Juan-Carlos Saiz

Open access · bronzeAbstract read
In one paragraph

Article in Journal of virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed
6.7field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

99 citing papers in PubMed, 150 citations in OpenAlex.

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  8. Cellular Biology: Virus-Host Interactions and RNA Structure and Function.Current topics in microbiology and immunology · 2026
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  10. Measles virus reprograms CD4Frontiers in cell and developmental biology · 2026
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39 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

Miguel A Martín-AcebesDepartment of Virology and Microbiology, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain.ORCID http://orcid.org/0000-0001-6015-3613
Teresa Merino-RamosDepartment of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain.
Ana-Belén BlázquezDepartment of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain.
Josefina CasasDepartment of Biomedicinal Chemistry, Institute for Advanced Chemistry of Catalonia (IQAC-CSIC), Barcelona, Spain.
Estela Escribano-RomeroDepartment of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain.
Francisco SobrinoDepartment of Virology and Microbiology, Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain fsobrino@cbm.csic.es jcsaiz@inia.es.
Juan-Carlos SaizDepartment of Biotechnology, Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA), Madrid, Spain fsobrino@cbm.csic.es jcsaiz@inia.es.
Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria · ESCentro de Biología Molecular Severo Ochoa · ESInstitute of Advanced Chemistry of Catalonia · ESUniversidad Autónoma de Madrid · ES

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

West Nile virus (WNV) is an emerging zoonotic mosquito-borne flavivirus responsible for outbreaks of febrile illness and meningoencephalitis. The replication of WNV takes place on virus-modified membranes from the endoplasmic reticulum of the host cell, and virions acquire their envelope by budding into this organelle. Consistent with this view, the cellular biology of this pathogen is intimately linked to modifications of the intracellular membranes, and the requirement for specific lipids, such as cholesterol and fatty acids, has been documented. In this study, we evaluated the impact of WNV infection on two important components of cellular membranes, glycerophospholipids and sphingolipids, by mass spectrometry of infected cells. A significant increase in the content of several glycerophospholipids (phosphatidylcholine, plasmalogens, and lysophospholipids) and sphingolipids (ceramide, dihydroceramide, and sphingomyelin) was noticed in WNV-infected cells, suggesting that these lipids have functional roles during WNV infection. Furthermore, the analysis of the lipid envelope of WNV virions and recombinant virus-like particles revealed that their envelopes had a unique composition. The envelopes were enriched in sphingolipids (sphingomyelin) and showed reduced levels of phosphatidylcholine, similar to sphingolipid-enriched lipid microdomains. Inhibition of neutral sphingomyelinase (which catalyzes the hydrolysis of sphingomyelin into ceramide) by either pharmacological approaches or small interfering RNA-mediated silencing reduced the release of flavivirus virions as well as virus-like particles, suggesting a role of sphingomyelin-to-ceramide conversion in flavivirus budding and confirming the importance of sphingolipids in the biogenesis of WNV. Importance: West Nile virus (WNV) is a neurotropic flavivirus spread by mosquitoes that can infect multiple vertebrate hosts, including humans. There is no specific vaccine or therapy against this pathogen licensed for human use. Since the multiplication of this virus is associated with rearrangements of host cell membranes, we analyzed the effect of WNV infection on different cellular lipids that constitute important membrane components. The levels of multiple lipid species were increased in infected cells, pointing to the induction of major alterations of cellular lipid metabolism by WNV infection. Interestingly, certain sphingolipids, which were increased in infected cells, were also enriched in the lipid envelope of the virus, thus suggesting a potential role during virus assembly. We further verified the role of sphingolipids in the production of WNV by means of functional analyses. This study provides new insight into the formation of flavivirus infectious particles and the involvement of sphingolipids in the WNV life cycle.

Indexed as

HeLa CellsHumansMass SpectrometryMembrane LipidsMicroscopy, FluorescenceSphingolipidsWest Nile virusMembrane LipidsSphingolipids

Identifiers

PMID25122799
PMCPMC4178726
OpenAlexW2107942229

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.