Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human secretory leukocyte protease inhibitor (SLPI), a serine protease inhibitor found concentrated in secretory fluids, has been postulated to participate in the body's natural defense against infection by the human immunodeficiency virus type-1 (HIV-1) by affecting trypsin-like enzymes on the surface of target cells. SLPI was evaluated for potential antiviral activity against laboratory, clinical and monocytotropic strains of HIV-1 in human T-cell lines, peripheral blood lymphocytes and monocyte/macrophage cultures. SLPI was tested in a single cycle of infection assay and under conditions in which SLPI was preincubated both with target cells and with virus and then maintained during the virus-to-cell adsorption phase and throughout the entire culture period. However, SLPI did not exert anti-HIV activity under any experimental conditions, and mechanistic studies showed SLPI to have no inhibitory activity on HIV-1 binding, reverse transcriptase or protease. Thus, SLPI exhibited no suggestive anti-HIV-1 activity.
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PMID:Human immunodeficiency virus type-1 (HIV-1) replication is unaffected by human secretory leukocyte protease inhibitor. 873 5

This review summarizes the data on the anti-human immunodeficiency virus (HIV) activity associated with saliva and the possible routes of oral transmission of HIV. Saliva can be passed from an HIV-infected individual to an uninfected person via sexual or non-sexual activities. The relative risk of HIV transmission through saliva is a subject of continuing concern for dental practitioners. HIV-infected individuals frequently have oral lesions that can cause bleeding and release of the virus into the oral cavity. In addition, viral p24 and HIV-1 RNA were detected in tonsils and adenoids even in asymptomatic seropositive individuals. Nevertheless, the potential HIV-infectivity of saliva is low, although both infectious HIV-1 and HIV DNA have been detected in saliva. This observation has led to the suggestion that saliva may contain factors that inhibit HIV-1 infectivity. At least two anti-HIV activities have been partially characterized: (i) physical entrapment of HIV by high-molecular-weight molecules (e.g., mucins), and (ii) inhibition of viral infection by soluble proteins. Several studies have indicated that, of the salivary proteins evaluated, recombinant secretory leukocyte protease inhibitor (rSLPI) could inhibit HIV-1 infection in macrophages at physiological concentrations. The anti-HIV activity of the serine protease inhibitor rSLPI is most likely due to its interaction with a cell-surface molecule(s) other than the primary HIV-1 receptor, CD4, and may involve (i) inhibition of cell-surface serine protease(s), and/or (ii) interaction with other human-specific co-factors essential for viral entry.
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PMID:The anti-HIV-1 activity associated with saliva. 906 56

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.
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PMID:Anatomic dissociation between HIV-1 and its endogenous inhibitor in mucosal tissues. 909 84

Infection of monocytes with human immunodeficiency virus type 1(Ba-L) (HIV-1(Ba-L)) is significantly inhibited by treatment with the serine protease inhibitor, secretory leukocyte protease inhibitor (SLPI). SLPI does not appear to act on virus directly, but rather the inhibitory activity is most likely due to interaction with the host cell. The current study was initiated to investigate how SLPI interacts with monocytes to inhibit infection. SLPI was found to bind to monocytes with high affinity to a single class of receptor sites (approximately 7,000 receptors per monocyte, K(D) = 3.6 nmol/L). The putative SLPI receptor was identified as a surface protein with a molecular weight of 55 +/- 5 kD. A well-characterized function of SLPI is inhibition of neutrophil elastase and cathepsin G. However, two SLPI mutants (or muteins) that contain single amino acid substitutions and exhibit greatly reduced protease inhibitory activity still bound to monocytes and retained anti-HIV-1 activity. SLPI consists of two domains, of which the C-terminal domain contains the protease inhibiting region. However, when tested independently, neither domain had potent anti-HIV-1 activity. SLPI binding neither prevented virus binding to monocytes nor attenuated the infectivity of any virus progeny that escaped inhibition by SLPI. A polymerase chain reaction (PCR)-based assay for newly generated viral DNA demonstrated that SLPI blocks at or before viral DNA synthesis. Therefore, it most likely inhibits a step of viral infection that occurs after virus binding but before reverse transcription. Taken together, the unique antiviral activity of SLPI, which may be independent of its previously characterized antiprotease activity, appears to reside in disruption of the viral infection process soon after virus binding.
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PMID:Inhibition of human immunodeficiency virus type 1 infectivity by secretory leukocyte protease inhibitor occurs prior to viral reverse transcription. 924 46

Saliva contains factors that inhibit infection with the human immunodeficiency virus type 1 (HIV-1) in vitro. One of these factors was recently identified as secretory leukocyte protease inhibitor (SLPI), a salivary protein which blocked HIV-1 infectivity of monocytes and primary T cells at physiologic concentrations (J Clin Invest 1995; 96: 456). Here, we confirm and extend the original report by demonstrating that SLPI protects primary monocytes and peripheral blood mononuclear cells against infection with HIV-1 Ba-L, IIIB and NL4-3. Thus, SLPI may provide a natural barrier against oral transmission of HIV-1.
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PMID:Secretory leukocyte protease inhibitor blocks infectivity of primary monocytes and mononuclear cells with both monocytotropic and lymphocytotropic strains of human immunodeficiency virus type I. 945 61

Sexually transmitted diseases, including trichomoniasis, are risk factors for acquisition of human immunodeficiency virus (HIV) infection. Enhancement mechanisms are unknown. Secretory leukocyte protease inhibitor (SLPI) from saliva appears to prevent transmission of HIV through inhibition of virus entry into monocytic cells in vitro. This study was undertaken to determine if secreted cysteine proteases of Trichomonas vaginalis degrade SLPI and render it nonfunctional. It was determined if SLPI levels were decreased in vaginal fluids from pregnant women infected with T. vaginalis. Isolated proteases were incubated with recombinant human SLPI, and the degradation was followed by Western analysis with SLPI antiserum. SLPI levels were measured by ELISA in vaginal fluids from women infected with T. vaginalis and uninfected controls. Cysteine proteases cleaved SLPI and rendered it nonfunctional. Median levels of SLPI from infected patients were 26% of those of controls (P <.005). The degradation of SLPI in association with trichomonal infection may increase the risk of HIV acquisition.
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PMID:Cysteine proteases of Trichomonas vaginalis degrade secretory leukocyte protease inhibitor. 972 51

One-third to two-thirds of maternal transmission of human immunodeficiency virus type 1 (HIV-1) infection to breast-fed infants can be attributed to ingestion of breast milk. The presence of HIV-1 as cell-free and as cell-associated virus in milk has been documented. Several substances in breast milk may be protective against transmission, including maternal anti-HIV antibodies, vitamin A, lactoferrin, and secretory leukocyte protease inhibitor. The portal of virus entry in the infant's gastrointestinal tract is unknown but may involve breaches in mucosal surfaces, transport across M cells, or direct infection of other epithelial cells, such as enterocytes. Timing of transmission of HIV-1 during lactation should be further clarified. An early rebound of plasma viremia after withdrawal of antiretrovirals was recently detected. This rebound may reduce the benefit of antiretroviral prophylaxis when women breast-feed their infants. Interventions should be viewed from the public health perspective of risks of infant morbidity and mortality associated with breast-feeding versus risks from formula-feeding.
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PMID:Transmission of human immunodeficiency virus type 1 through breast-feeding: how can it be prevented? 1009 7

The oral cavity represents a unique site for mucosal transmission of human immunodeficiency virus type 1 (HIV-1). Unlike other mucosal sites, the oral cavity is rarely a site of HIV transmission despite detectable virus in saliva and oropharyngeal tissues of infected persons. One reason for this apparent paradox is the presence of endogenous mucosal antiviral factors. Innate inhibitory molecules, such as virus-specific antibodies, mucins, thrombospondin, and soluble proteins, have been identified and partially characterized from saliva. A recent addition to the growing list is secretory leukocyte protease inhibitor (SLPI), an approximately 12-kDa non-glycosylated protein found in serous secretions. Physiologic concentrations of SLPI potently protect adherent monocytes and activated peripheral blood mononuclear cells against HIV-1 infection. SLPI levels in saliva and semen but not breast milk approximate levels required for inhibition in vitro. Characterization of SLPI and other endogenous antiviral molecules may enhance our understanding of factors influencing mucosal HIV-1 transmission.
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PMID:Endogenous mucosal antiviral factors of the oral cavity. 1009 13

Secretory leukocyte protease inhibitor (SLPI) has been found to possess activity against the human immunodeficiency virus type 1 (HIV-1) in vitro at physiological concentrations. A study was undertaken to evaluate SLPI levels in human saliva and plasma among HIV-positive (HIV(+)) patients with various HIV-1 viral loads in comparison to uninfected controls. Whole blood in EDTA and unstimulated saliva samples were collected from 37 HIV(+) patients, of whom 20 had a history of intravenous drug abuse (IVDA). Control samples were collected from 20 appropriate age- and sex-matched HIV-1-negative individuals. SLPI was estimated from both saliva and serum samples by an enzyme-linked immunosorbent assay. HIV viral load was determined using a quantitative reverse transcription-PCR. SLPI levels were increased 16.7% in plasma and 10.3% in saliva among HIV(+) patients in comparison to uninfected controls. SLPI levels were increased 5.9% in saliva and 3.9% in plasma among HIV(+) patients with a high viral load (>10,000 copies/ml) as compared to patients with a low viral load (<400 copies/ml). Only 23% of patients with a high viral load used combination therapy with protease inhibitor drugs, whereas 92.9% of HIV(+) patients with a low viral load used protease inhibitors. SLPI levels did not differ significantly among the IVDA patients, patients with different viral loads, or patients using protease inhibitor drugs. There was a statistically significant increase in SLPI levels in saliva among HIV patients in comparison to non-HIV-infected controls. An increase in SLPI levels among HIV(+) patients may be a natural consequence of HIV pathogenesis and an important factor in preventing oral transmission of HIV, but this increase may not be evident during plasma viremia in patients with a high viral load.
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PMID:Enhanced secretory leukocyte protease inhibitor in human immunodeficiency virus type 1-infected patients. 1054 68

Human milk contains important immunological factors that protect the breast from infection and are thought to protect infants from infection, including human immunodeficiency virus (HIV) infection. Human milk immunological factors have not been well characterized in HIV-infected lactating women. Lysozyme, secretory leukocyte protease inhibitor (SLPI), sodium (an indicator of mastitis), and HIV were measured in breast milk of 334 HIV-infected women at 6 weeks postpartum. Women with mastitis, as indicated by elevated breast milk sodium concentrations, had higher median levels lysozyme (290 vs 221 mg/L, p < 0.04), SLPI (38 vs 19 mg/L, p < 0.0001) and HIV (920 copies/mL vs undetectable, p < 0.0001) compared with women without mastitis. Lower total plasma carotenoid levels (p < 0.02) and higher maternal HIV load (p < 0.006) by quartile were risk factors for mastitis. Mastitis, as indicated by elevated breast milk sodium levels, is associated with high concentrations of immunological factors and higher HIV load in breast milk.
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PMID:Mastitis and immunological factors in breast milk of human immunodeficiency virus-infected women. 1077 80


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