title: Herpes simplex virus-induced epithelial damage and susceptibility to human immunodeficiency virus type 1 infection in human cervical organ culture.
abstract: Normal human premenopausal cervical tissue has been used to derive primary cell populations and to establish ex vivo organ culture systems to study infections with herpes simplex virus (HSV-1 or HSV-2) and human immunodeficiency virus type 1 (HIV-1). Infection with either HSV-1 or HSV-2 rapidly induced multinuclear giant cell formation and widespread damage in mucosal epithelial cells. Subsequent exposure of the damaged mucosal surfaces to HIV-1 revealed frequent co-localization of HSV and HIV-1 antigens. The short-term organ culture system provides direct experimental support for the epidemiological findings that pre-existing sexually transmitted infections, including primary and recurrent herpes virus infections at mucosal surfaces, represent major risk factors for acquisition of primary HIV-1 infection. Epithelial damage in combination with pre-existing inflammation, as described here for overtly normal human premenopausal cervix, creates a highly susceptible environment for the initiation and establishment of primary HIV-1 infection in the sub-mucosa of the cervical transformation zone.
authors.affiliation: Department of Microbiology, University of Minnesota, Minneapolis, Minnesota, United States of America.
authors.forename: Julie E
authors.initials: JE
authors.lastname: Horbul
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Schmechel
authors.forename: Barrie R L
authors.initials: BR
authors.lastname: Miller
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Rice
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Southern
mesh_terms: D000956:Antigens, Viral / Q000276:immunology; D002449:Cell Aggregation; D002478:Cells, Cultured; D002584:Cervix Uteri / Q000473:pathology* / Q000821:virology*; D004198:Disease Susceptibility; D004847:Epithelial Cells / Q000473:pathology / Q000821:virology; D004848:Epithelium / Q000473:pathology* / Q000821:virology*; D005260:Female; D005347:Fibroblasts / Q000473:pathology / Q000821:virology; D015726:Giant Cells / Q000473:pathology / Q000821:virology; D015658:HIV Infections / Q000150:complications / Q000473:pathology / Q000821:virology*; D015497:HIV-1 / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications / Q000473:pathology; D009092:Mucous Membrane / Q000473:pathology / Q000821:virology; D009924:Organ Culture Techniques; D017697:Premenopause; D018139:Simplexvirus / Q000276:immunology / Q000502:physiology*
chemical_list: D000956:Antigens, Viral