Evidence map›Paper›PMID 29709018›Full record

ArticlePLoS pathogens2018

Phospholipase A2 activity during the replication cycle of the flavivirus West Nile virus.

Susann Liebscher, Rebecca L Ambrose, Turgut E Aktepe, Andrea Mikulasova, Julia E Prier, Leah K Gillespie, Adam J Lopez-Denman, Thusitha W T Rupasinghe, Dedreia Tull, Malcolm J McConville and 1 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
6.4field-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

34 citing papers in PubMed, 44 citations in OpenAlex.

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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

11 authors at 3 institutions in 1 country.

Susann LiebscherDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.ORCID 0000-0001-6401-8160
Rebecca L AmbroseDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
Turgut E AktepeDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
Andrea MikulasovaDepartment of Microbiology, La Trobe University, Melbourne, VIC, Australia.
Julia E PrierDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.ORCID 0000-0002-2653-6300
Leah K GillespieDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.
Adam J Lopez-DenmanDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.ORCID 0000-0001-6051-6381
Thusitha W T RupasingheMetabolomics Australia, Bio21 Molecular Science and Biotechnology Institute, Department of Biochemistry and Molecular Biology at University of Melbourne, Melbourne, VIC, Australia.
Dedreia TullMetabolomics Australia, Bio21 Molecular Science and Biotechnology Institute, Department of Biochemistry and Molecular Biology at University of Melbourne, Melbourne, VIC, Australia.
Malcolm J McConvilleMetabolomics Australia, Bio21 Molecular Science and Biotechnology Institute, Department of Biochemistry and Molecular Biology at University of Melbourne, Melbourne, VIC, Australia.
Jason M MackenzieDepartment of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia.ORCID 0000-0001-6613-8350
Peter Doherty Institute · AUThe University of Melbourne · AULa Trobe University · AU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Positive-sense RNA virus intracellular replication is intimately associated with membrane platforms that are derived from host organelles and comprised of distinct lipid composition. For flaviviruses, such as West Nile virus strain Kunjin virus (WNVKUN) we have observed that these membrane platforms are derived from the endoplasmic reticulum and are rich in (at least) cholesterol. To extend these studies and identify the cellular lipids critical for WNVKUN replication we utilized a whole cell lipidomics approach and revealed an elevation in phospholipase A2 (PLA2) activity to produce lyso-phosphatidylcholine (lyso-PChol). We observed that the PLA2 enzyme family is activated in WNVKUN-infected cells and the generated lyso-PChol lipid moieties are sequestered to the subcellular sites of viral replication. The requirement for lyso-PChol was confirmed using chemical inhibition of PLA2, where WNVKUN replication and production of infectious virus was duly affected in the presence of the inhibitors. Importantly, we could rescue chemical-induced inhibition with the exogenous addition of lyso-PChol species. Additionally, electron microscopy results indicate that lyso-PChol appears to contribute to the formation of the WNVKUN membranous replication complex (RC); particularly affecting the morphology and membrane curvature of vesicles comprising the RC. These results extend our current understanding of how flaviviruses manipulate lipid homeostasis to favour their own intracellular replication.

Indexed as

Virus ReplicationAnimalsCells, CulturedChlorocebus aethiopsCricetinaeEndoplasmic ReticulumKidneyMembrane LipidsPhospholipases A2Vero CellsWest Nile FeverWest Nile virusMembrane LipidsPhospholipases A2

Identifiers

PMID29709018
PMCPMC5945048
OpenAlexW2801933523

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.