title: The meningeal lymphatic system: a route for HIV brain migration?
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.
authors.affiliation: Bioinfoexperts, LLC, Thibodaux, LA, 70301, USA. susanna@bioinfox.com.
authors.forename: Susanna L
authors.initials: SL
authors.lastname: Lamers
authors.affiliation: Bioinfoexperts, LLC, Thibodaux, LA, 70301, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Rose
authors.affiliation: University of Hawaii, Honolulu, HI, USA.
authors.forename: Lishomwa C
authors.initials: LC
authors.lastname: Ndhlovu
authors.affiliation: University of Florida, Gainesville, FL, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Nolan
authors.affiliation: University of Florida, Gainesville, FL, USA.
authors.forename: Marco
authors.initials: M
authors.lastname: Salemi
authors.affiliation: University of California and the AIDS and Cancer Specimen Resource, San Francisco, CA, USA.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Maidji
authors.affiliation: University of California and the AIDS and Cancer Specimen Resource, San Francisco, CA, USA.
authors.forename: Cheryl A
authors.initials: CA
authors.lastname: Stoddart
authors.affiliation: University of California and the AIDS and Cancer Specimen Resource, San Francisco, CA, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: McGrath
mesh_terms: D015526:AIDS Dementia Complex / Q000276:immunology / Q000473:pathology / Q000821:virology*; D001812:Blood-Brain Barrier / Q000276:immunology / Q000821:virology; D001921:Brain / Q000276:immunology / Q000821:virology*; D002465:Cell Movement; D018925:Chemokines / Q000096:biosynthesis / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D004730:Endothelium, Vascular / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D008208:Lymphatic System / Q000276:immunology / Q000821:virology*; D008264:Macrophages / Q000276:immunology / Q000821:virology; D008578:Meninges / Q000276:immunology / Q000821:virology*; D009000:Monocytes / Q000276:immunology / Q000821:virology*; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D053586:Virus Internalization
chemical_list: D018925:Chemokines
keywords: HIV brain infection; Lymphatic system; Macrophage-targeted therapy; Meninges; Neurological disease