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Cited by 112Barrier Structure and Function StudiesT-cell and Retrovirus StudiesHIV Research and Treatment

Alteration of Blood–Brain Barrier Integrity by Retroviral Infection

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Afonso, Philippe V., Ozden, Simona, Cumont, Marie-Christine, Seilhean, Danielle, Cartier, Luis, Rezaie, Payam, Mason, Sarah, Lambert, Sophie +6 more·2008·PLoS Pathogens
DOI 10.1371/journal.ppat.1000205PMC PMC2575404
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Abstract

The blood-brain barrier (BBB), which forms the interface between the blood and the cerebral parenchyma, has been shown to be disrupted during retroviral-associated neuromyelopathies. Human T Lymphotropic Virus (HTLV-1) Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a slowly progressive neurodegenerative disease associated with BBB breakdown. The BBB is composed of three cell types: endothelial cells, pericytes and astrocytes. Although astrocytes have been shown to be infected by HTLV-1, until now, little was known about the susceptibility of BBB endothelial cells to HTLV-1 infection and the impact of such an infection on BBB function. We first demonstrated that human cerebral endothelial cells express the receptors for HTLV-1 (GLUT-1, Neuropilin-1 and heparan sulfate proteoglycans), both in vitro, in a human cerebral endothelial cell line, and ex vivo, on spinal cord autopsy sections from HAM/TSP and non-infected control cases. In situ hybridization revealed HTLV-1 transcripts associated with the vasculature in HAM/TSP. We were able to confirm that the endothelial cells could be productively infected in vitro by HTLV-1 and that blocking of either HSPGs, Neuropilin 1 or Glut1 inhibits this process. The expression of the tight-junction proteins within the HTLV-1 infected endothelial cells was altered. These cells were no longer able to form a functional barrier, since BBB permeability and lymphocyte passage through the monolayer of endothelial cells were increased. This work constitutes the first report of susceptibility of human cerebral endothelial cells to HTLV-1 infection, with implications for HTLV-1 passage through the BBB and subsequent deregulation of the central nervous system homeostasis. We propose that the susceptibility of cerebral endothelial cells to retroviral infection and subsequent BBB dysfunction is an important aspect of HAM/TSP pathogenesis and should be considered in the design of future therapeutics strategies.

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  • Viral infections in general downregulate TJ proteins and promote chemokine production and vascular cell adhesion molecule 1 (VCAM-1) expression in brain endothelial cells, thereby weakening the BBB and facilitating entry into the brain.

    “Viral infections in general downregulate TJ proteins and promote chemokine production and vascular cell adhesion molecule 1 (VCAM-1) expression in brain endothelial cells, thereby weakening the BBB and facilitating entry into the brain (5, 212, 399, 613).”

    From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [5]

    The Results section (‘Impairment of BBB functions following infection by HTLV-1’; page unavailable) reports reduced ZO-1 and one occludin isoform in HTLV-1-infected brain endothelial cells. The Discussion reports impaired barrier function and increased lymphocyte migration, but this is evidence about HTLV-1, not viral infections in general. Our copy does not establish chemokine production or VCAM-1 expression in these cells. (LLM, conf=0.88)

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Cited by

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Authors
Afonso, P. V., Ozden, S., Cumont, M.-C., Seilhean, D., Cartier, L., Rezaie, P., Mason, S., Lambert, S., Huerre, M., Gessain, A., Couraud, P.-O., Pique, C., Ceccaldi, P.-E., & Romero, I. A.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Institut Pasteur (FR)
  • Pitié-Salpêtrière Hospital (FR)
  • University of Chile (CL)
  • The Open University (GB)
Corresponding author
  • Ceccaldi, Pierre-Emmanuel
  • Romero, Ignacio A.
ORCID
Venue
PLoS Pathogens
Publisher
Public Library of Science (PLoS)
Published
2008-11-14
Volume
4
Issue
11
Pages
e1000205
ISSN
  • 1553-7366 (ISSN-L)
  • 1553-7374
DOI
10.1371/journal.ppat.1000205
PMC
PMC2575404
OpenAlex
W2111040181
Cited by
112
References
1
Citations by year
2026: 1 · 2025: 5 · 2024: 8 · 2023: 6 · 2022: 5 · 2021: 5 · 2020: 12 · 2019: 6 · 2018: 11 · 2017: 7 · 2016: 5 · 2015: 6 · 2014: 4 · 2013: 7 · 2012: 9
FWCI
3.08
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS Pathogens (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Open Research Online - ORO (The Open University) (acceptedVersion)
  • HAL (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Universidad de Chile (submittedVersion)
Funders
Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and Retrovirus Studies
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
Keywords
blood-brain barrier, HTLV-1, HAM/TSP, retroviral infection, brain endothelial cells, viral receptor expression, GLUT1, neuropilin-1, heparan sulfate proteoglycans, tight junction proteins, blood-brain barrier permeability, neurodegeneration pathogenesis
MeSH terms
Autopsy, Blood-Brain Barrier, Cell Line, Humans, Receptors, Virus, Retroviridae Infections, Spinal Cord, Human T-lymphotropic virus 1, Paraparesis, Tropical Spastic, Tight Junctions, Endothelial Cells

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