title: Anatomic dissociation between HIV-1 and its endogenous inhibitor in mucosal tissues.
abstract: The rarity of oral transmission of human immunodeficiency virus (HIV)-1 by saliva suggests the absence of HIV-1 in the oral cavity and/or the presence of viral inhibitory molecules. We analyzed salivary gland tissues from 55 individuals with acquired immune deficiency syndrome (AIDS) for the presence of HIV-1 by in situ hybridization and detected the virus in more than 30% of these salivary glands. These data, together with previous demonstrations of HIV-1 in oral secretions, implicate a key role for an anti-viral molecule(s) in suppressing transmission. Thus, we focused on the characterization and localization of the endogenous antiviral molecule secretory leukocyte protease inhibitor (SLPI), which inhibits HIV-1 infection in vitro. Expression of SLPI transcripts was evident in submandibular, parotid, and minor salivary glands from both HIV-1-infected and seronegative subjects. Gene expression was reflected by similar levels of SLPI protein by immunohistochemical analysis in the tissues and by enzyme-linked immunosorbent assay in the saliva. However, although SLPI accumulated in acinar cells or ductal epithelium, HIV-1 transcripts did not, and these viral transcripts were identified only in mononuclear cells within the salivary gland stroma. By in situ hybridization, we found no evidence of productive HIV-1 infection of salivary gland epithelium. Thus, HIV-1 was frequently identified in salivary gland tissue, but the virus was found in interstitial mononuclear cells only and did not co-localize with SLPI. Once within the oral cavity, HIV-1 exposure to antiviral levels of SLPI may impede infection of additional target cells, contributing to the virtual absence of oral transmission of HIV-1 by saliva. These studies emphasize the importance of innate, endogenous inhibitors of HIV-1, particularly SLPI, as effective inhibitors of HIV-1 transmission.
authors.affiliation: Laboratory of Immunology, National Institute of Dental Research, Bethesda, MD 20892-4352, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Wahl
authors.forename: P
authors.initials: P
authors.lastname: Worley
authors.forename: W
authors.initials: W
authors.lastname: Jin
authors.forename: T B
authors.initials: TB
authors.lastname: McNeely
authors.forename: S
authors.initials: S
authors.lastname: Eisenberg
authors.forename: C
authors.initials: C
authors.lastname: Fasching
authors.forename: J M
authors.initials: JM
authors.lastname: Orenstein
authors.forename: E N
authors.initials: EN
authors.lastname: Janoff
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000201:enzymology / Q000276:immunology; D000998:Antiviral Agents / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D007700:Kinetics; D009061:Mouth Mucosa / Q000201:enzymology* / Q000821:virology; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012463:Saliva / Q000737:chemistry / Q000201:enzymology / Q000821:virology; D012469:Salivary Glands / Q000737:chemistry / Q000201:enzymology* / Q000821:virology; D012471:Salivary Proteins and Peptides / Q000096:biosynthesis / Q000235:genetics; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors / Q000737:chemistry / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D053491:Proteinase Inhibitory Proteins, Secretory; D011506:Proteins; C506814:SLPI protein, human; D012471:Salivary Proteins and Peptides; D053481:Secretory Leukocyte Peptidase Inhibitor; D015842:Serine Proteinase Inhibitors