Evidence map›Paper›PMID 19036821›Full record

ArticleJournal of virology2009

Low-pH triggering of human metapneumovirus fusion: essential residues and importance in entry.

Rachel M Schowalter, Andres Chang, Jessica G Robach, Ursula J Buchholz, Rebecca Ellis Dutch

Open access · greenAbstract read
In one paragraph

Article in Journal of virology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed
3.4field-weighted citation impact, top 8% 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

57 citing papers in PubMed, 89 citations in OpenAlex.

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  12. IFITM3 Restricts Human Metapneumovirus Infection.The Journal of infectious diseases · 2018
    Article
  13. Article
  14. Frontiers in microbiology · 2018
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Paramyxovirus Glycoproteins and the Membrane Fusion Process.Current clinical microbiology reports · 2016
    Article
  20. Article
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

5 authors at 3 institutions in 1 country.

Rachel M SchowalterDepartment of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, Kentucky 40536-0509, USA.
Andres Chang
Jessica G Robach
Ursula J Buchholz
Rebecca Ellis Dutch
University of Kentucky · USNational Institute of Allergy and Infectious Diseases · USNorthwestern University · US

Funding

SV5 and Hendra virus F protein promoted membrane fusionR01AI051517 · NIAID · UNIVERSITY OF KENTUCKY · PI DUTCH, REBECCA E. · 2002 to 2019
$4.4M
HMPV Fusion protein-host cell interactionsR21AI074783 · NIAID · UNIVERSITY OF KENTUCKY · PI DUTCH, REBECCA E. · 2007 to 2008
$399k
NIAID NIH HHS 1R21AI074783-01NIAID NIH HHS R01 AI051517NIAID NIH HHS R21 AI074783
6 · The paper itself

Abstract

Human metapneumovirus (HMPV) is a significant respiratory pathogen classified in the Pneumovirinae subfamily of the paramyxovirus family. Recently, we demonstrated that HMPV F protein-promoted cell-cell fusion is stimulated by exposure to low pH, in contrast to what is observed for other paramyxovirus F proteins. In the present study, we examined the potential role of histidine protonation in HMPV F fusion and investigated the role of low pH in HMPV viral entry. Mutagenesis of the three ectodomain histidine residues of the HMPV F protein demonstrated that the mutation of a histidine in the heptad repeat B linker domain (H435) ablated fusion activity without altering cell surface expression or proteolytic processing significantly. Modeling of the HMPV F protein revealed several basic residues surrounding this histidine residue, and the mutation of these residues also reduced fusion activity. These results suggest that electrostatic repulsion in the heptad repeat B linker region may contribute to the triggering of HMPV F. In addition, we examined the effect of inhibitors of endosomal acidification or endocytosis on the entry of a recombinant green fluorescent protein-expressing HMPV. Interestingly, chemicals that raise the pH of endocytic vesicles resulted in a 30 to 50% decrease in HMPV infection, while the inhibitors of endocytosis reduced infection by as much as 90%. These data suggest that HMPV utilizes an endocytic entry mechanism, in contrast to what has been hypothesized for most paramyxoviruses. In addition, our results indicate that HMPV uses the low pH of the endocytic pathway to enhance infectivity, though the role of low pH likely differs from classically described mechanisms.

Indexed as

Hydrogen-Ion ConcentrationMembrane FusionAnimalsChlorocebus aethiopsGenes, ReporterHumansMetapneumovirusVero Cells

Identifiers

PMID19036821
PMCPMC2620907
OpenAlexW2112931025

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.