Evidence map›Paper›PMID 32109948›Full record

ArticlePLoS pathogens2020

Reovirus uses macropinocytosis-mediated entry and fast axonal transport to infect neurons.

Pavithra Aravamudhan, Krishnan Raghunathan, Jennifer Konopka-Anstadt, Amrita Pathak, Danica M Sutherland, Bruce D Carter, Terence S Dermody

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
0.7field-weighted citation impact, top 17% 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

23 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Exosomal transmission of viruses, a two-edged biological sword.Cell communication and signaling : CCS · 2023
    Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Article
  14. Article
  15. Loss of MAPK8IP3 Affects Endocytosis in Neurons.Frontiers in cellular neuroscience · 2022
    Article
  16. Review
  17. Review
  18. Long-distance regressive signaling in neural development and disease.Wiley interdisciplinary reviews. Developmental biology · 2021
    Review
  19. Review
  20. 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

7 authors at 2 institutions in 1 country.

Pavithra AravamudhanDepartment of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Krishnan RaghunathanDepartment of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Jennifer Konopka-AnstadtDepartment of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.ORCID 0000-0002-4062-5350
Amrita PathakDepartment of Biochemistry and Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.ORCID 0000-0003-1396-9868
Danica M SutherlandDepartment of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.
Bruce D CarterDepartment of Biochemistry and Vanderbilt Brain Institute, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America.ORCID 0000-0002-3242-6634
Terence S DermodyDepartment of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, United States of America.ORCID 0000-0003-1853-8741
University of Pittsburgh · USVanderbilt University · US

Funding

MOLECULAR BASIS OF REOVIRUS PATHOGENESISR01AI038296 · NIAID · VANDERBILT UNIVERSITY · PI DERMODY, TERENCE S. · 1996 to 2019
$3.3M
MOLECULAR PARASITOLOGY TRAINING PROGRAMT32AI007281 · NIAID · MEHARRY MEDICAL COLLEGE · PI NDE, PIUS N · 1985 to 2025
$3.2M
The role of the glial engulfment receptor Jedi1 in regulating sensory neuron functionR01NS102365 · NINDS · VANDERBILT UNIVERSITY · PI CARTER, BRUCE D · 2018 to 2022
$1.7M
NIAID NIH HHS R01 AI038296NIAID NIH HHS T32 AI007281NINDS NIH HHS R01 NS102365
6 · The paper itself

Abstract

Several barriers protect the central nervous system (CNS) from pathogen invasion. Yet viral infections of the CNS are common and often debilitating. Understanding how neurotropic viruses co-opt host machinery to overcome challenges to neuronal entry and transmission is important to combat these infections. Neurotropic reovirus disseminates through neural routes and invades the CNS to cause lethal encephalitis in newborn animals. To define mechanisms of reovirus neuronal entry and directional transport, we used primary neuron cultures, which reproduce in vivo infection patterns displayed by different reovirus serotypes. Treatment of neurons with small-molecule inhibitors of different endocytic uptake pathways allowed us to discover that the cellular machinery mediating macropinocytosis is required for reovirus neuronal entry. This mechanism of reovirus entry differs from clathrin-mediated endocytosis, which is used by reovirus to invade non-neuronal cells. Analysis of reovirus transport and release from isolated soma or axonal termini of neurons cultivated in microfluidic devices indicates that reovirus is capable of retrograde but only limited anterograde neuronal transmission. The dynamics of retrograde reovirus movement are consistent with fast axonal transport coordinated by dynein along microtubules. Further analysis of viral transport revealed that multiple virions are transported together in axons within non-acidified vesicles. Reovirus-containing vesicles acidify after reaching the soma, where disassembly of virions and release of the viral core into the cytoplasm initiates replication. These results define mechanisms of reovirus neuronal entry and transport and establish a foundation to identify common host factors used by neuroinvasive viruses. Furthermore, our findings emphasize consideration of cell type-specific entry mechanisms in the tailored design of neurotropic viruses as tracers, oncolytic agents, and delivery vectors.

Indexed as

AnimalsAxonal TransportAxonsCell LineCentral Nervous SystemCytoplasmEndocytosisMaleMiceMicrotubulesNeuronsPinocytosisPrimary Cell CultureRatsRats, Sprague-DawleyReoviridae

Identifiers

PMID32109948
PMCPMC7065821
OpenAlexW3007744741

What OpenQuestion holds

Textmetadata
LicenceCC0
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.