title: Deciphering Human Cell-Autonomous Anti-HSV-1 Immunity in the Central Nervous System.
abstract: Herpes simplex virus 1 (HSV-1) is a common virus that can rarely invade the human central nervous system (CNS), causing devastating encephalitis. The permissiveness to HSV-1 of the various relevant cell types of the CNS, neurons, astrocytes, oligodendrocytes, and microglia cells, as well as their response to viral infection, has been extensively studied in humans and other animals. Nevertheless, human CNS cell-based models of anti-HSV-1 immunity are of particular importance, as responses to any given neurotropic virus may differ between humans and other animals. Human CNS neuron cell lines as well as primary human CNS neurons, astrocytes, and microglia cells cultured/isolated from embryos or cadavers, have enabled the study of cell-autonomous anti-HSV-1 immunity in vitro. However, the paucity of biological samples and their lack of purity have hindered progress in the field, which furthermore suffers from the absence of testable primary human oligodendrocytes. Recently, the authors have established a human induced pluripotent stem cells (hiPSCs)-based model of anti-HSV-1 immunity in neurons, oligodendrocyte precursor cells, astrocytes, and neural stem cells, which has widened the scope of possible in vitro studies while permitting in-depth explorations. This mini-review summarizes the available data on human primary and iPSC-derived CNS cells for anti-HSV-1 immunity. The hiPSC-mediated study of anti-viral immunity in both healthy individuals and patients with viral encephalitis will be a powerful tool in dissecting the disease pathogenesis of CNS infections with HSV-1 and other neurotropic viruses.
authors.affiliation: Rockefeller Branch, St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University , New York, NY , USA.
authors.forename: Fabien G
authors.initials: FG
authors.lastname: Lafaille
authors.affiliation: Rockefeller Branch, St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University , New York, NY , USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ciancanelli
authors.affiliation: The Center for Stem Cell Biology, Developmental Biology Program, Sloan-Kettering Institute for Cancer Research , New York, NY , USA.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Studer
authors.affiliation: Department of Microbiology-Immunology, Northwestern University Feinberg School of Medicine , Chicago, IL , USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Smith
authors.affiliation: Division of Immunology, Boston Children's Hospital and Harvard Medical School , Boston, MA , USA.
authors.forename: Luigi
authors.initials: L
authors.lastname: Notarangelo
authors.affiliation: Rockefeller Branch, St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University , New York, NY , USA ; Howard Hughes Medical Institute , New York, NY , USA ; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children , Paris , France ; Imagine Institute, Paris Descartes University , Paris , France ; Pediatric Hematology-Immunology Unit, Necker Hospital for Sick Children , Paris , France.
authors.forename: Jean-Laurent
authors.initials: JL
authors.lastname: Casanova
authors.affiliation: Rockefeller Branch, St. Giles Laboratory of Human Genetics of Infectious Diseases, The Rockefeller University , New York, NY , USA ; Laboratory of Human Genetics of Infectious Diseases, Necker Branch, INSERM U1163, Necker Hospital for Sick Children , Paris , France ; Imagine Institute, Paris Descartes University , Paris , France.
authors.forename: Shen-Ying
authors.initials: SY
authors.lastname: Zhang
keywords: CNS; HSE; HSV-1; TLR3; antiviral immunity; disease modeling; hiPSCs; interferons