Endogenous salivary inhibitors of Human Immunodeficiency Virus

Shugars, Diane C.; Alexander, Audrey; Fu, Kaisong; Freel, Stephanie A.

doi:10.1016/s0003-9969(99)00003-5

Cited by 45 publications

(55 citation statements)

References 61 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The physiologically relevant substrates of NEP in the brain and spinal cord are enkephalins and SP (10,22). The breakdown of these NEP-sensitive peptides was measured by using 3 H substrate and chromatographic analysis for SP, as above, or using natural substrate and RP-HPLC or RIA analyses for ME. Peptidase inhibitors were used to confirm that the neuropeptide fragments detected are metabolic products formed through enzymatic action ex vivo (fresh spinal slices) or in vitro (spinal membranes).…”

Section: Sialorphin An Inhibitor Of the Sp And Me Catabolism By Spinmentioning

confidence: 99%

See 1 more Smart Citation

Sialorphin, a natural inhibitor of rat membrane-bound neutral endopeptidase that displays analgesic activity

Rougeot

Messaoudi

Hermitte

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Sialorphin is an exocrine and endocrine signaling mediator, which has been identified by a genomic approach. It is synthesized predominantly in the submandibular gland and prostate of adult rats in response to androgen steroids and is released locally and systemically in response to stress. We now demonstrate that the cell surface molecule to which sialorphin binds in vivo in the rat kidney is the membrane-anchored neutral endopeptidase (neprilysin; NEP, EC 3.4.24.11). NEP plays an important role in nervous and peripheral tissues, as it turns off several peptide-signaling events at the cell surface. We show that sialorphin prevents spinal and renal NEP from breaking down its two physiologically relevant substrates, substance P and Met-enkephalin in vitro. Sialorphin inhibited the breakdown of substance P with an IC50 of 0.4 -1 M and behaved as a competitive inhibitor. In vivo, i.v. sialorphin elicited potent antinociceptive responses in two behavioral rat models of injury-induced acute and tonic pain, the pin-pain test and formalin test. The analgesia induced by 100 -200 g͞kg doses of sialorphin required the activation of -and ␦-opioid receptors, consistent with the involvement of endogenous opioid receptors in enkephalinergic transmission. We conclude that sialorphin protects endogenous enkephalins released after nociceptive stimuli by inhibiting NEP in vivo. Sialorphin is a natural systemically active regulator of NEP activity. Furthermore, our study provides evidence that it is a physiological modulator of pain perception after injury and might be the progenitor of a new class of therapeutic molecules.

show abstract

Section: Sialorphin An Inhibitor Of the Sp And Me Catabolism By Spinmentioning

confidence: 99%

“…These mediate many local and peripheral functions participating in the adaptive responses to stress (1)(2)(3)(4)(5).…”

mentioning

confidence: 99%

Sialorphin, a natural inhibitor of rat membrane-bound neutral endopeptidase that displays analgesic activity

Rougeot

Messaoudi

Hermitte

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…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). Anti-HIV-1 activity has been detected consistently in whole saliva.…”

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

View full text Add to dashboard Cite

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.

show abstract

“…33 The current study demonstrates that both normal human and macaque whole saliva are capable of inhibiting SIV and HIV infection in vitro using a sensitive, standardized assay. These data suggest that the same innate antiviral components identified in human saliva may also be present in macaque saliva, and that the inhibitory activities of these salivary components are not limited to HIV-1.…”

Section: Discussionmentioning

confidence: 71%

“…5 Multiple endogenous human salivary factors with specific and nonspecific mechanisms of anti-HIV activity have been described since Fultz first demonstrated inhibition of HIV infection in vitro by whole human and chimpanzee saliva. 10,33,34 Despite the widespread use of SIV-infected rhesus macaques as an animal model for HIV transmission and pathogenesis, few studies have utilized this model to evaluate the inhibitory components of macaque saliva. One study, by Nagashunmugam et al, was unable to demonstrate any inhibitory activity of human submandibular saliva against HIV-2 ROD or SIV Mac239 infection of HUT78 cells in vitro, as measured by reverse transcriptase activity at 7 days postinfection.…”

Section: Discussionmentioning

confidence: 99%

Characterization of SIV in the Oral Cavity andin VitroInhibition of SIV by Rhesus Macaque Saliva

Thomas

Lacour

Kozlowski

et al. 2010

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

Human immunodeficiency virus (HIV) infections are rarely acquired via an oral route in adults. Previous studies have shown that human whole saliva inhibits HIV infection in vitro, and multiple factors present in human saliva have been shown to contribute to this antiviral activity. Despite the widespread use of simian immunodeficiency virus (SIV)-infected rhesus macaques as models for HIV pathogenesis and transmission, few studies have monitored SIV in the oral cavity of infected rhesus macaques and evaluated the viral inhibitory capacity of macaque saliva. Utilizing a cohort of rhesus macaques infected with SIV Mac251 , we monitored virus levels and genotypic diversity in the saliva throughout the course of the disease; findings were similar to previous observations in HIV-infected humans. An in vitro infectivity assay was utilized to measure inhibition of HIV/SIV infection by normal human and rhesus macaque whole saliva. Both human and macaque saliva were capable of inhibiting HIV and SIV infection. The inhibitory capacity of saliva samples collected from a cohort of animals postinfection with SIV increased over the course of disease, coincident with the development of SIV-specific antibodies in the saliva. These findings suggest that both innate and adaptive factors contribute to inhibition of SIV by whole macaque saliva. This work also demonstrates that SIV-infected rhesus macaques provide a relevant model to examine the innate and adaptive immune responses that inhibit HIV/SIV in the oral cavity.

show abstract

Endogenous salivary inhibitors of Human Immunodeficiency Virus

Cited by 45 publications

References 61 publications

Sialorphin, a natural inhibitor of rat membrane-bound neutral endopeptidase that displays analgesic activity

Sialorphin, a natural inhibitor of rat membrane-bound neutral endopeptidase that displays analgesic activity

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

Characterization of SIV in the Oral Cavity andin VitroInhibition of SIV by Rhesus Macaque Saliva

Contact Info

Product

Resources

About