title: Restrictions that control herpes simplex virus type 1 infection in mouse brain ex vivo.
abstract: Elucidating the cellular and molecular factors governing herpes simplex virus type 1 (HSV-1) neurotropism is a prerequisite for understanding HSV-1 encephalitis and for targeting HSV-1-derived vectors for gene transfer to the brain. Earlier we had described an ex vivo system of mouse brain slices and demonstrated a selective and unique infection pattern, mostly around the ventricles. Here, we examined tissue factors controlling HSV-1 infection of brain slices. We demonstrated that heparan sulphate, while an important factor, does not determine the infection pattern. Hyaluronic acid, but not collagen, appears to enhance HSV-1 brain infection. To investigate whether tissue distribution of viral receptors determines the infection pattern, we examined transcription of herpes virus entry mediator and nectin-1 receptor genes in infected and uninfected brain regions. Both the infected and the uninfected regions express the receptors. We also explored the influence of intra-cellular factors. HSV-1 does not preferentially infect proliferating cells in the brain slices, despite its predilection to the ventricular zones. To delineate the step at which the HSV-1 infection cascade is restricted, mRNA was isolated following tissue infection, and transcription of the immediate-early and late viral genes was evaluated. The results indicated that HSV-1 genes are not expressed in regions that do not express a viral reporter gene. Therefore, we conclude that tissue resistance to infection is associated with a block at or prior to the immediate-early mRNA synthesis. Taken together, using the ex vivo system of organotypic culture we describe here extra-cellular and intra-cellular restriction levels of HSV-1 brain infection.
authors.affiliation: Department of Biochemistry, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.|Laboratory of Neurovirology, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Meytal
authors.initials: M
authors.lastname: Cohen
authors.affiliation: Department of Biochemistry, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.|Laboratory of Neurovirology, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Efrat
authors.initials: E
authors.lastname: Braun
authors.affiliation: Department of Biochemistry, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.|Laboratory of Neurovirology, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Yael
authors.initials: Y
authors.lastname: Tsalenchuck
authors.affiliation: Department of Biochemistry, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Amos
authors.initials: A
authors.lastname: Panet
authors.affiliation: Department of Neurology, Rabin Medical Center, Campus Beilinson, Petach Tikva, Israel.|Laboratory of Neurovirology, IMRIC, The Hebrew University-Hadassah Medical School, Jerusalem, Israel.
authors.forename: Israel
authors.initials: I
authors.lastname: Steiner
mesh_terms: D000818:Animals; D001921:Brain / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D004195:Disease Models, Animal; D020803:Encephalitis, Herpes Simplex / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D020869:Gene Expression Profiling; D018259:Herpesvirus 1, Human / Q000276:immunology* / Q000472:pathogenicity*; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D012367:RNA, Viral / Q000096:biosynthesis; D011991:Receptors, Virus / Q000096:biosynthesis; D056189:Viral Tropism; D014779:Virus Replication
chemical_list: D012367:RNA, Viral; D011991:Receptors, Virus