Secretory leukocyte protease inhibitor: inhibition of human immunodeficiency virus-1 infection of monocytic THP-1 cells by a newly cloned protein

Shine, Nancy R.; Wang, Susan C.; Konopka, Krystyna; Burks, Elizabeth A.; Düzgüneş, Nejat; Whitman, Christian P.

doi:10.1016/s0045-2068(02)00008-1

Cited by 27 publications

(20 citation statements)

References 54 publications

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“…In 1995, McNeely and coworkers showed that infection of adherent primary monocytes with HIV-1 was significantly suppressed in the presence of human saliva. Of the proteins present in the saliva, only SLPI was found to have antiretroviral activity at physiological concentrations (0.1 to 10 g/ml) (25) (22,39). These discrepancies are attributed to either changes during synthesis of rSLPI molecules or differences in the intrinsic properties of the target cells, such as isolation, culture, and infection conditions; donor variations; and levels of macrophage maturation at the time of infection (22,39).…”

Section: Anti-hiv-1 Activitymentioning

confidence: 99%

“…Of the proteins present in the saliva, only SLPI was found to have antiretroviral activity at physiological concentrations (0.1 to 10 g/ml) (25) (22,39). These discrepancies are attributed to either changes during synthesis of rSLPI molecules or differences in the intrinsic properties of the target cells, such as isolation, culture, and infection conditions; donor variations; and levels of macrophage maturation at the time of infection (22,39). In addition, four in vitro studies have demonstrated SLPI anti-HIV-1 activity in nonmacrophage cells that included peripheral blood mononuclear cells, purified primary T cells, and SupT1 cells, a lymphocyte-derived tumor cell line (19,25,41,45).…”

Section: Anti-hiv-1 Activitymentioning

confidence: 99%

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Anti-Inflammatory and Antimicrobial Roles of Secretory Leukocyte Protease Inhibitor

Doumas¹,

2005

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Section: Anti-hiv-1 Activitymentioning

confidence: 99%

Section: Anti-hiv-1 Activitymentioning

confidence: 99%

Anti-Inflammatory and Antimicrobial Roles of Secretory Leukocyte Protease Inhibitor

Doumas¹,

2005

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“…Reports of no or inconsistent inhibition by two research groups (25,55) prompted a reexamination of SLPI antiviral activity. SLPI inhibition in vitro was subsequently confirmed by several groups (19,48,51), including one group that initially reported negative findings (47) with various cell culture models and HIV-1 isolates having different subtypes and chemokine coreceptor usage patterns. Additional evidence for SLPI antiviral activity came from African studies of perinatal HIV-1 transmission in which high transmission rates were associated with low levels (below 0.1 g/ml, the MIC required in vitro) (33) of vaginal SLPI in infected mothers (40) and salivary SLPI in breast-fed babies (11).…”

mentioning

confidence: 93%

Human Immunodeficiency Virus Type 1 Stimulates the Expression and Production of Secretory Leukocyte Protease Inhibitor (SLPI) in Oral Epithelial Cells: a Role for SLPI in Innate Mucosal Immunity

Jana¹,

Gray

Shugars

2005

J Virol

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The innate immune response is a key barrier against pathogenic microorganisms such as human immunodeficiency virus type 1 (HIV-1). Because HIV-1 is rarely transmitted orally, we hypothesized that oral epithelial cells participate in the innate immune defense against this virus. We further hypothesized that secretory leukocyte protease inhibitor (SLPI), a 12-kDa mucosal antiviral protein, is a component of the host immune response to this virus. Here we demonstrated constitutive expression and production of SLPI in immortalized human oral keratinocytes. Brief exposure of cells to HIV-1 BaL and HXB2 significantly increased SLPI mRNA and protein production compared to that in mock-exposed cells (P < 0.01), as evaluated by real-time quantitative reverse transcription-PCR and enzyme-linked immunosorbent assay. HIV-1-mediated stimulation of SLPI occurred at the transcriptional level, was dose and time dependent, was elicited by heat-inactivated and infectious viruses, and did not depend on cellular infection. Experiments with purified retroviral proteins showed that the stimulatory effect was induced specifically by external envelope glycoproteins from HIV-1 and simian immunodeficiency virus. SLPI responsiveness to HIV-1 was also observed in an unrelated oral epithelial cell line and in normal (nonimmortalized) human oral epithelial cells isolated from healthy uninfected gingival tissues. In this first report of SLPI regulation by HIV-1, we show that the expression and production of the antimicrobial and anti-inflammatory protein can be stimulated in oral epithelial cells by the virus through interactions with gp120 in the absence of direct infection. These findings indicate that SLPI is a component of the oral mucosal response to HIV-1.

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“…Endogenous anti-HIV-1 activity has been demonstrated in whole, parotid, and submandibular/sublingual (sm/sl) saliva, colostrum, whole milk, and seminal plasma (1,11,13,24,29,32,38,45,46,51) but not in cerebrospinal fluid or urine (38). The incidence of oral HIV-1 transmission is very low and can be attributed both to endogenous salivary factors that prevent oral excretion of transmissible levels of virus (45,47,48) and to lysis of HIV-infected cells due to the hypotonicity of saliva (2,3).…”

mentioning

confidence: 99%

Comparison of Human Immunodeficiency Virus Type 1-Specific Inhibitory Activities in Saliva and Other Human Mucosal Fluids

Kazmi

Naglik

Sweet

et al. 2006

Clin Vaccine Immunol

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Several human mucosal fluids are known to possess an innate ability to inhibit human immunodeficiency virus type 1 (HIV-1) infection and replication in vitro. This study compared the HIV-1 inhibitory activities of several mucosal fluids, whole, submandibular/sublingual (sm/sl), and parotid saliva, breast milk, colostrum, seminal plasma, and cervicovaginal secretions, from HIV-1-seronegative donors by using a 3-day microtiter infection assay. A wide range of HIV-1 inhibitory activity was exhibited in all mucosal fluids tested, with some donors exhibiting high levels of activity while others showed significantly lower levels. Colostrum, whole milk, and whole saliva possessed the highest levels of anti-HIV-1 activity, seminal fluid, cervicovaginal secretions, and sm/sl exhibited moderate levels, and parotid saliva consistently demonstrated the lowest levels of HIV-1 inhibition. Fast protein liquid chromatography gel filtration studies revealed the presence of at least three distinct peaks of inhibitory activity against HIV-1 in saliva and breast milk. Incubation of unfractionated and fractionated whole saliva with antibodies raised against human lactoferrin (hLf), secretory leukocyte protease inhibitor (SLPI), and, to a lesser extent, MG2 (high-molecular-weight mucinous glycoprotein) reduced the HIV-1 inhibitory activity significantly. The results suggest that hLf and SLPI are two key components responsible for HIV-1 inhibitory activity in different mucosal secretions. The variation in HIV inhibitory activity between the fluids and between individuals suggests that there may be major differences in susceptibility to HIV infection depending both on the individual and on the mucosal fluid involved.

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Secretory leukocyte protease inhibitor: inhibition of human immunodeficiency virus-1 infection of monocytic THP-1 cells by a newly cloned protein

Cited by 27 publications

References 54 publications

Anti-Inflammatory and Antimicrobial Roles of Secretory Leukocyte Protease Inhibitor

Anti-Inflammatory and Antimicrobial Roles of Secretory Leukocyte Protease Inhibitor

Human Immunodeficiency Virus Type 1 Stimulates the Expression and Production of Secretory Leukocyte Protease Inhibitor (SLPI) in Oral Epithelial Cells: a Role for SLPI in Innate Mucosal Immunity

Comparison of Human Immunodeficiency Virus Type 1-Specific Inhibitory Activities in Saliva and Other Human Mucosal Fluids

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