Anatomic dissociation between HIV-1 and its endogenous inhibitor in mucosal tissues
| Autor: | S M, Wahl, P, Worley, W, Jin, T B, McNeely, S, Eisenberg, C, Fasching, J M, Orenstein, E N, Janoff |
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| Rok vydání: | 1997 |
| Předmět: |
Acquired Immunodeficiency Syndrome
Serine Proteinase Inhibitors Mouth Mucosa Proteinase Inhibitory Proteins Secretory Proteins Antiviral Agents Immunohistochemistry Salivary Glands Kinetics stomatognathic system HIV-1 Humans Secretory Leukocyte Peptidase Inhibitor Salivary Proteins and Peptides Saliva Research Article |
| Zdroj: | The American journal of pathology. 150(4) |
| ISSN: | 0002-9440 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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