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Mucosal inhibitors of HIV-1 = Sluznični zaviralci virusa imunske pomjanjkljivosti pri človeku (HIV-1)
Wahl, Sharon M. ...
Introduction. Human immunodeficiency virus (HIV-1), the causative agent of theacquired immunodeficiency syndrome (AIDS), is commonly transmitted by bloodand also at mucosal surfaces. However, the ...oral mucosa appears relativelyresistant to HIV-1 transmission and evidence foes not of this apparent protected environment within the oral cavity, considerable effort hasbeen expended to identify the unique features associated with this mucosal site which are responsible for limitinge HIV-1 transmission. Among the identified inhibitors are HIV-1-specific antibodies generated at mucosal surfaces in the oral cavity. Saliva from HIV-1 seronegative donors, lacking HIV-1 antibodies, also showed significant neutralizing activity to HIV-1, suggesting that innate defense factorst may also contribute to viral resistance. Through isolation and screening of a battery of salivary components for their ability to inhibit HIV-1 infection in vitro assays, the high molecular weight mucins, large glycoproteins secreted by the acinar cellsof the submandibular glands, were found to aggregate and entrap viral particles. Another molecule isolated from saliva that was found to block HIV-1infection of mononuclear cells in culture was identified as secretory leukocyte protease ihibitor (SLPI). At concentrations routinety present in oral secretions, this 12kD single chain polypeptide, produced by acinar cells in parotid and submandibular glands, inhibits HIV-1 infection. The mechanism whereby SLPI inhibits infection by HIV-1 appears to involve an interaction with the cellular hosts of the virus and not the virus intself. SLPI binding to monocytes, a key target of HIV-1, is specific, and time-, temperature,-, concentraion- and pH-dependent. Binding data reveal the presence of approximately 7000 binding sites per monocyte. In vitro, a single transient exposure of mononuclear cells to physiological conceptions of SLPI cause prolonged resistance to infection.(Abstract truncated at 2000 characters.
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