Evidence map›Paper›PMID 22398316›Full record

ArticleThe Journal of general virology2012

West Nile virus-induced disruption of the blood-brain barrier in mice is characterized by the degradation of the junctional complex proteins and increase in multiple matrix metalloproteinases.

Kelsey Roe, Mukesh Kumar, Stephanie Lum, Beverly Orillo, Vivek R Nerurkar, Saguna Verma

Abstract read
In one paragraph

Article in The Journal of general virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
126citing papers in PubMed, 1 pooled it
15.4field-weighted citation impact, top 1% 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

126 citing papers in PubMed, 1 synthesis or guideline pooled it, 174 citations in OpenAlex.

  1. Determination of Burn Size in Mouse Models of Burn Injury: A Scoping Review of Studies Leveraging Scald and Contact Burns.Journal of burn care & research : official publication of the American Burn Association · 2025
    Pooled it
  2. Differential effects of Tat proteins derived from HIV-1 subtypes B and recombinant CRF02_AG on human brain microvascular endothelial cells: implications for blood-brain barrier dysfunction.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2014
    Trial
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  19. Unraveling the complexities of neurotropic virus infection and immune evasion.Microbiology and molecular biology reviews : MMBR · 2025
    Review
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66 more citing papers are in PubMed but not listed here.

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

6 authors at 1 institution in 1 country.

Kelsey RoeDepartment of Tropical Medicine, Medical Microbiology and Pharmacology, Pacific Center for Emerging Infectious Diseases Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96813, USA.
Mukesh KumarDepartment of Tropical Medicine, Medical Microbiology and Pharmacology, Pacific Center for Emerging Infectious Diseases Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96813, USA.
Stephanie LumDepartment of Tropical Medicine, Medical Microbiology and Pharmacology, Pacific Center for Emerging Infectious Diseases Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96813, USA.
Beverly OrilloDepartment of Tropical Medicine, Medical Microbiology and Pharmacology, Pacific Center for Emerging Infectious Diseases Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96813, USA.
Vivek R NerurkarDepartment of Tropical Medicine, Medical Microbiology and Pharmacology, Pacific Center for Emerging Infectious Diseases Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96813, USA.
Saguna VermaDepartment of Tropical Medicine, Medical Microbiology and Pharmacology, Pacific Center for Emerging Infectious Diseases Research, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, Hawaii 96813, USA.
University of Hawaiʻi at Mānoa · US

Funding

WORLDWIDE EPIDEMIOLOGY &EPIZOOTIOLOGY OF HANTAVIRUSG12RR003061 · NCRR · UNIVERSITY OF HAWAII AT MANOA · PI OSTRANDER, GARY K · 1986 to 2011
$32.3M
UHI COBRE: P3: GROUP A STREPT IN RELATION TO ACUTE RHEUMATIC FEVER IN HAWAIIP20RR018727 · NCRR · UNIVERSITY OF HAWAII AT MANOA · PI VERMA, SAGUNA · 2003 to 2011
$13.8M
Pacific Center for Emerging Infectious Diseases ResearchP20GM103516 · NIGMS · UNIVERSITY OF HAWAII AT MANOA · PI YANAGIHARA, RICHARD · 2012 to 2014
$6.1M
NCRR NIH HHS G12 RR003061NCRR NIH HHS G12RR003061NCRR NIH HHS P20 RR018727NCRR NIH HHS P20RR018727NIGMS NIH HHS 8P20GM1033S16-08NIGMS NIH HHS P20 GM103516
6 · The paper itself

Abstract

West Nile virus (WNV) encephalitis is characterized by neuroinflammation, neuronal loss and blood-brain barrier (BBB) disruption. However, the mechanisms associated with the BBB disruption are unclear. Complex interactions between the tight junction proteins (TJP) and the adherens junction proteins (AJP) of the brain microvascular endothelial cells are responsible for maintaining the BBB integrity. Herein, we characterized the relationship between the BBB disruption and expression kinetics of key TJP, AJP and matrix metalloproteinases (MMPs) in the mice brain. A dramatic increase in the BBB permeability and extravasation of IgG was observed at later time points of the central nervous system (CNS) infection and did not precede virus-CNS entry. WNV-infected mice exhibited significant reduction in the protein levels of the TJP ZO-1, claudin-1, occludin and JAM-A, and AJP β-catenin and vascular endothelial cadherin, which correlated with increased levels of MMP-1, -3 and -9 and infiltrated leukocytes in the brain. Further, intracranial inoculation of WNV also demonstrated increased extravasation of IgG in the brain, suggesting the role of virus replication in the CNS in BBB disruption. These data suggest that altered expression of junction proteins is a pathological event associated with WNV infection and may explain the molecular basis of BBB disruption. We propose that WNV initially enters CNS without altering the BBB integrity and later virus replication in the brain initiates BBB disruption, allowing enhanced infiltration of immune cells and contribute to virus neuroinvasion via the 'Trojan-horse' route. These data further implicate roles of multiple MMPs in the BBB disruption and strategies to interrupt this process may influence the WNV disease outcome.

Indexed as

AnimalsBlood-Brain BarrierHumansMatrix Metalloproteinase 1Matrix Metalloproteinase 3Matrix Metalloproteinase 9Membrane ProteinsMiceMice, Inbred C57BLProteolysisTight JunctionsUp-RegulationWest Nile FeverWest Nile virusMatrix Metalloproteinase 1Matrix Metalloproteinase 3Matrix Metalloproteinase 9Membrane Proteins

Identifiers

PMID22398316
PMCPMC3755517
OpenAlexW2161039036

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.