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J Neurovirol. 2016 Jun;22(3):275-81. doi: 10.1007/s13365-015-0399-y. Epub 2015 Nov 16.

The meningeal lymphatic system: a route for HIV brain migration?

Author information

1
Bioinfoexperts, LLC, Thibodaux, LA, 70301, USA. susanna@bioinfox.com.
2
Bioinfoexperts, LLC, Thibodaux, LA, 70301, USA.
3
University of Hawaii, Honolulu, HI, USA.
4
University of Florida, Gainesville, FL, USA.
5
University of California and the AIDS and Cancer Specimen Resource, San Francisco, CA, USA.

Abstract

Two innovative studies recently identified functional lymphatic structures in the meninges that may influence the development of HIV-associated neurological disorders (HAND). Until now, blood vessels were assumed to be the sole transport system by which HIV-infected monocytes entered the brain by bypassing a potentially hostile blood-brain barrier through inflammatory-mediated semi-permeability. A cascade of specific chemokine signals promote monocyte migration from blood vessels to surrounding brain tissues via a well-supported endothelium, where the cells differentiate into tissue macrophages capable of productive HIV infection. Lymphatic vessels on the other hand are more loosely organized than blood vessels. They absorb interstitial fluid from bodily tissues where HIV may persist and exchange a variety of immune cells (CD4(+) T cells, monocytes, macrophages, and dendritic cells) with surrounding tissues through discontinuous endothelial junctions. We propose that the newly discovered meningeal lymphatics are key to HIV migration among viral reservoirs and brain tissue during periods of undetectable plasma viral loads due to suppressive combinational antiretroviral therapy, thus redefining the migration process in terms of a blood-lymphatic transport system.

KEYWORDS:

HIV brain infection; Lymphatic system; Macrophage-targeted therapy; Meninges; Neurological disease

PMID:
26572785
PMCID:
PMC4868798
DOI:
10.1007/s13365-015-0399-y
[Indexed for MEDLINE]
Free PMC Article

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