Author/Editor		Wahl, Sharon M; Wild, Teresa K; Sanneman, Thomas C; Janoff, Edward N
Title		Mucosal inhibitors of HIV-1
Translated title		Sluznični zaviralci virusa imunske pomanjkljivosti pri človeku (HIV-1)
Type		članek
Source		Zdrav Vestn
Vol. and No.		Letnik 67, št. Suppl 2
Publication year		1998
Volume		str. II-91-4
Language		eng
Abstract		Introduction. Human immunodeficiency virus (HIV-1), the causative agent of the acquired immunodeficiency syndrome (AIDS), is commonly transmitted by blood and also at mucosal surfaces. However, the oral mucosa appears relatively resistant to HIV-1 transmission and evidence foes not of this apparent protected environment within the oral cavity, considerable effort has been 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 cells of the submandibular glands, were found to aggregate and entrap viral particles. Another molecule isolated from saliva that was found to block HIV-1 infection 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.
Summary		Izhodišča. Virus človeške imunske pomanjkljivosti (HIV-1), ki povzroča AIDS, se prenaša preko krvi in površin sluznic. Različne raziskave so pokazale, da je ustna sluznica relativno odporna proti HIV-1 in da je slina zelo redko tekočina, preko katere bi se prenašala okužba s HIV-1. Slina vsebuje mnogo proteinov, ki lahko vplivajo na prenos okužbe z virusi. Avtorji podrobno opisujejo sekretorni levkocitni proteinazni inhibitor (SLPI), ki je v slini vedno v taki količini, ki uspešno zavre infekcijo monocitov z virusom HIV-1, SLPI so našli, razen v slinavkah in slini, tudi v epitelju drugih žlez in na površini sluznic, ki so odprte zunanjemu okolju. SLPI se ne veže na virus ali njegove sestavne dele, temveč na površino monocitov in limbocitov, ki izražajo CD4 receptorje in koreceptorje: SLPI tako v fizioloških koncentracijah povzroči odpornost proti virusni okužbi, vendar ne more preprečiti razmnoževanja virusa v že okuženih celicah. SLPI so našli v slini HIV okuženih in neokuženih oseb. SLPI je v serumu v taki koncentraciji, ki ne omogoča protivirusnega delovanja zato ne preseneča, da so našli virus v 38% v serumu in samo v 1% v slini okuženih oseb. Natančna fiziološka vloga SLPI-ja ni poznana. Deluje kot inhibitor serumskih proteinaz, ima protivirusno, pa tudi protibakterijsko delovanje. Izlgeda, da je pomemben pri imunološki obrambi sluznic, saj ga najdemo v normalni koncentraciji že v slini novorojenčkov. Zaključki. Avtorji kažejo na možnost, da bi z lokalnim ali spodbujanjem izločanja SLPI-ja zvišali imunološko obrambo proti virusom in bakterijami, ki ogrožajo sluznice.
Descriptors		MOUTH MUCOSA SALIVA HIV-1 IMMUNITY, MUCOSAL PROTEASE INHIBITORS