Evidence map›Paper›PMID 33515546›Full record

ArticleThe Journal of biological chemistry

Ceramide synthase 2 deletion decreases the infectivity of HIV-1.

Eric Barklis, Ayna Alfadhli, Jennifer E Kyle, Lisa M Bramer, Kent J Bloodsworth, Robin Lid Barklis, Hans C Leier, R Max Petty, Iris D Zelnik, Thomas O Metz and 2 more

Open access · goldAbstract read
In one paragraph

Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
1.7field-weighted citation impact, top 16% 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

15 citing papers in PubMed, 25 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. HIV and SIV Envelope Glycoproteins Interact with Glycolipids and Lipids.International journal of molecular sciences · 2023
    Article
  8. Neutral sphingomyelinase 2 is required for HIV-1 maturation.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Ceramide and Related Molecules in Viral Infections.International journal of molecular sciences · 2021
    Review
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

12 authors at 3 institutions in 2 countries.

Eric BarklisDepartment of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, Oregon, USA. Electronic address: barklis@ohsu.edu.
Ayna AlfadhliDepartment of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, Oregon, USA.
Jennifer E KyleBiological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory (PNNL), Richland, Washington, USA.
Lisa M BramerComputing and Analytics Division, National Security Directorate PNNL, Richland, Washington, USA.
Kent J BloodsworthBiological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory (PNNL), Richland, Washington, USA.
Robin Lid BarklisDepartment of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, Oregon, USA.
Hans C LeierDepartment of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, Oregon, USA.
R Max PettyDepartment of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, Oregon, USA.
Iris D ZelnikDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
Thomas O MetzBiological Sciences Division, Earth and Biological Sciences Directorate, Pacific Northwest National Laboratory (PNNL), Richland, Washington, USA.
Anthony H FutermanDepartment of Biomolecular Sciences, Weizmann Institute of Science, Rehovot, Israel.
Fikadu G TafesseDepartment of Molecular Microbiology and Immunology, Oregon Health and Sciences University, Portland, Oregon, USA. Electronic address: tafesse@ohsu.edu.
Oregon Health & Science University · USPacific Northwest National Laboratory · USWeizmann Institute of Science · IL

Funding

Pacific Northwest Advanced Compound Identification CoreU2CES030170 · NIEHS · BATTELLE PACIFIC NORTHWEST LABORATORIES · PI METZ, THOMAS O · 2018 to 2021
$4.6M
HIV-1 Gag Precursor Protein InteractionsR01AI152579 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI BARKLIS, ERIC W · 2020 to 2024
$2.5M
Determining the role of sphingolipids in Mycobacterium tuberculosis infectionR01AI141549 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI TAFESSE, FIKADU G. · 2020 to 2025
$2.4M
Determining the role of host lipids in Zika virus infectionR21AI133631 · NIAID · OREGON HEALTH & SCIENCE UNIVERSITY · PI TAFESSE, FIKADU G. · 2017 to 2018
$424k
NIAID NIH HHS R01 AI141549NIAID NIH HHS R01 AI152579NIAID NIH HHS R21 AI133631NIEHS NIH HHS U2C ES030170
6 · The paper itself

Abstract

The lipid composition of HIV-1 virions is enriched in sphingomyelin (SM), but the roles that SM or other sphingolipids (SLs) might play in the HIV-1 replication pathway have not been elucidated. In human cells, SL levels are regulated by ceramide synthase (CerS) enzymes that produce ceramides, which can be converted to SMs, hexosylceramides, and other SLs. In many cell types, CerS2, which catalyzes the synthesis of very long chain ceramides, is the major CerS. We have examined how CerS2 deficiency affects the assembly and infectivity of HIV-1. As expected, we observed that very long chain ceramide, hexosylceramide, and SM were reduced in CerS2 knockout cells. CerS2 deficiency did not affect HIV-1 assembly or the incorporation of the HIV-1 envelope (Env) protein into virus particles, but it reduced the infectivites of viruses produced in the CerS2-deficient cells. The reduced viral infection levels were dependent on HIV-1 Env, since HIV-1 particles that were pseudotyped with the vesicular stomatitis virus glycoprotein did not exhibit reductions in infectivity. Moreover, cell-cell fusion assays demonstrated that the functional defect of HIV-1 Env in CerS2-deficient cells was independent of other viral proteins. Overall, our results indicate that the altered lipid composition of CerS2-deficient cells specifically inhibit the HIV-1 Env receptor binding and/or fusion processes.

Indexed as

Gene DeletionCeramidesHEK293 CellsHIV-1HIV InfectionsHumansMembrane ProteinsSphingosine N-AcyltransferaseTumor Suppressor ProteinsVirus InternalizationCeramidesCERS2 protein, humanMembrane ProteinsSphingosine N-AcyltransferaseTumor Suppressor Proteinsceramideceramide synthasefusion proteinHIVsphingolipid

Identifiers

PMID33515546
PMCPMC7949126
OpenAlexW3121560679

What OpenQuestion holds

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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.