title: Periluminal Distribution of HIV-Binding Target Cells and Gp340 in the Oral, Cervical and Sigmoid/Rectal Mucosae: A Mapping Study.
abstract: Studies have shown that the transmission of HIV is most likely to occur via rectal or vaginal routes, and rarely through oral exposure. However, the mechanisms of virus entry at mucosal surfaces remain incompletely understood. Prophylactic strategies against HIV infection may be attainable once gaps in current knowledge are filled. To address these gaps, we evaluated essentially normal epithelial surfaces and mapped the periluminal distribution of CD4+ HIV target cells, including T cells and antigen-presenting cells, and an HIV-binding molecule gp340 that can be expressed by epithelial cells in secreted and cell-associated forms. Immunohistochemistry for CD4, CD16, CD3, CD1a and gp340 in human oral, rectal/sigmoid and cervical mucosal samples from HIV-negative subjects demonstrated that periluminal HIV target cells were more prevalent at rectal/sigmoid and endocervical surfaces lined by simple columnar epithelium, than at oral and ectocervical surfaces covered by multilayered stratified squamous epithelium (p<0.001). gp340 expression patterns at these sites were also distinct and strong in oral minor salivary gland acini and ducts, including ductal saliva, in individual rectum/sigmoid and endocervix periluminar columnar cells, and in ectocervix squamous cells. Only weak expression was noted in the oral non-ductal squamous epithelium. We conclude that periluminal HIV target cells, together with periluminal epithelial cell-associated gp340 appear to be most accessible for HIV transmission at rectal/sigmoid and endocervical surfaces. Our data help define vulnerable structural features of mucosal sites exposed to HIV.
authors.affiliation: Faculty of Medicine, Division of Experimental Medicine, McGill University, Montreal, Quebec, Canada.
authors.forename: Mariia
authors.initials: M
authors.lastname: Patyka
authors.affiliation: NYU College of Dentistry, Department of Basic Sciences, HIV/AIDS Research Program (HARP), New York, New York, United States of America; NYU School of Medicine, Infectious Disease, New York, New York, United States of America.
authors.forename: Daniel
authors.initials: D
authors.lastname: Malamud
authors.affiliation: Medicine (Infectious Disease), Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Drew
authors.initials: D
authors.lastname: Weissman
authors.affiliation: NYU College of Dentistry, Department of Basic Sciences, HIV/AIDS Research Program (HARP), New York, New York, United States of America.
authors.forename: William R
authors.initials: WR
authors.lastname: Abrams
authors.affiliation: Oral Health and Diagnostic Sciences, College of Dental Medicine, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Zoya
authors.initials: Z
authors.lastname: Kurago
mesh_terms: D000938:Antigen-Presenting Cells / Q000378:metabolism / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D002135:Calcium-Binding Proteins; D002584:Cervix Uteri / Q000378:metabolism / Q000821:virology*; D012809:Colon, Sigmoid / Q000378:metabolism / Q000821:virology*; D004268:DNA-Binding Proteins; D004847:Epithelial Cells / Q000378:metabolism / Q000821:virology; D004848:Epithelium / Q000378:metabolism / Q000821:virology; D005260:Female; D006678:HIV / Q000378:metabolism*; D015658:HIV Infections / Q000378:metabolism* / Q000635:transmission; D006801:Humans; D009092:Mucous Membrane / Q000378:metabolism / Q000821:virology*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012007:Rectum / Q000378:metabolism / Q000821:virology*; D025521:Tumor Suppressor Proteins; D014621:Vagina / Q000378:metabolism / Q000821:virology
chemical_list: D002135:Calcium-Binding Proteins; C108174:DMBT1 protein, human; D004268:DNA-Binding Proteins; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins