Evidence map›Paper›PMID 33647064›Full record

ArticlePLoS pathogens2021

Glycoprotein N-linked glycans play a critical role in arenavirus pathogenicity.

Takaaki Koma, Cheng Huang, Adrian Coscia, Steven Hallam, John T Manning, Junki Maruyama, Aida G Walker, Milagros Miller, Jeanon N Smith, Michael Patterson and 2 more

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.1field-weighted citation impact, top 10% 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

17 citing papers in PubMed, 27 citations in OpenAlex.

  1. Review
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  5. Article
  6. Strategies of rational and structure-driven vaccine design for Arenaviruses.Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases · 2024
    Review
  7. Article
  8. Article
  9. Entry inhibitors as arenavirus antivirals.Frontiers in microbiology · 2024
    Review
  10. Article
  11. Article
  12. Review
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  14. Article
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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

12 authors at 2 institutions in 1 country.

Takaaki KomaDepartment of Pathology, University of Texas Medical Branch at Galveston, Texas, United States of America.
Cheng HuangDepartment of Pathology, University of Texas Medical Branch at Galveston, Texas, United States of America.ORCID 0000-0001-5402-353X
Adrian CosciaDepartment of Microbiology, Harvard Medical School, Boston, Massachusetts, United States of America.ORCID 0000-0002-6836-9993
Steven HallamDepartment of Pathology, University of Texas Medical Branch at Galveston, Texas, United States of America.ORCID 0000-0002-3351-007X
John T ManningDepartment of Pathology, University of Texas Medical Branch at Galveston, Texas, United States of America.ORCID 0000-0002-2130-2054
Junki MaruyamaDepartment of Pathology, University of Texas Medical Branch at Galveston, Texas, United States of America.ORCID 0000-0003-0088-4793
Aida G WalkerDepartment of Pathology, University of Texas Medical Branch at Galveston, Texas, United States of America.ORCID 0000-0002-3922-0604
Milagros MillerDepartment of Pathology, University of Texas Medical Branch at Galveston, Texas, United States of America.
Jeanon N SmithDepartment of Pathology, University of Texas Medical Branch at Galveston, Texas, United States of America.
Michael PattersonDepartment of Pathology, University of Texas Medical Branch at Galveston, Texas, United States of America.ORCID 0000-0002-8701-3722
Jonathan AbrahamDepartment of Microbiology, Harvard Medical School, Boston, Massachusetts, United States of America.ORCID 0000-0002-7937-3920
Slobodan PaesslerDepartment of Pathology, University of Texas Medical Branch at Galveston, Texas, United States of America.ORCID 0000-0002-2213-9551
The University of Texas Medical Branch at Galveston · USHarvard University · US

Funding

Medical Scientist Training ProgramT32GM007753 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WALENSKY, LOREN DAVID · 1985 to 2021
$50.0M
NIGMS NIH HHS T32 GM007753
6 · The paper itself

Abstract

Several arenaviruses cause hemorrhagic fevers in humans with high case fatality rates. A vaccine named Candid#1 is available only against Junin virus (JUNV) in Argentina. Specific N-linked glycans on the arenavirus surface glycoprotein (GP) mask important epitopes and help the virus evade antibody responses. However the role of GPC glycans in arenavirus pathogenicity is largely unclear. In a lethal animal model of hemorrhagic fever-causing Machupo virus (MACV) infection, we found that a chimeric MACV with the ectodomain of GPC from Candid#1 vaccine was partially attenuated. Interestingly, mutations resulting in acquisition of N-linked glycans at GPC N83 and N166 frequently occurred in late stages of the infection. These glycosylation sites are conserved in the GPC of wild-type MACV, indicating that this is a phenotypic reversion for the chimeric MACV to gain those glycans crucial for infection in vivo. Further studies indicated that the GPC mutant viruses with additional glycans became more resistant to neutralizing antibodies and more virulent in animals. On the other hand, disruption of these glycosylation sites on wild-type MACV GPC rendered the virus substantially attenuated in vivo and also more susceptible to antibody neutralization, while loss of these glycans did not affect virus growth in cultured cells. We also found that MACV lacking specific GPC glycans elicited higher levels of neutralizing antibodies against wild-type MACV. Our findings revealed the critical role of specific glycans on GPC in arenavirus pathogenicity and have important implications for rational design of vaccines against this group of hemorrhagic fever-causing viruses.

Indexed as

AnimalsAntibodies, NeutralizingAntibodies, ViralArenavirusArenaviruses, New WorldHemorrhagic Fever, AmericanHumansJunin virusViral VaccinesAntibodies, NeutralizingAntibodies, ViralViral Vaccines

Identifiers

PMID33647064
PMCPMC7951981
OpenAlexW3135098056

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.