Human Submandibular Saliva Inhibits Human Immunodeficiency Virus Type 1 Infection by Displacing Envelope Glycoprotein gp120 from the Virus

Nagashunmugam, Thandavarayan; Malamud, Daniel; Davis, Cheryl; Abrams, William R.; Friedman, Harvey M.

doi:10.1086/314511

Cited by 61 publications

(60 citation statements)

References 33 publications

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“…SP-D is therefore potentially present together with CRP-ductin/gp-340 in the lung and throughout the gastrointestinal tract where it can interact both with phospholipids and microorganisms. Partial purified submandibular saliva containing agglutinin inhibits HIV type 1 infection by displacing envelope glycoprotein gp120 from the virus [31]. This indicates that gp-340 and CRPductin could potentially interact not only with bacteria but also with virus, and thereby have a function similar to the function of SP-D in innate immunity.…”

Section: Discussionmentioning

confidence: 98%

CRP‐ductin, the mouse homologue of gp‐340/deleted in malignant brain tumors 1 (DMBT1), binds gram‐positive and gram‐negative bacteria and interacts with lung surfactant protein D

et al. 2003

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CRP-ductin is a protein expressed mainly by mucosal epithelial cells in the mouse. Sequence homologies indicate that CRP-ductin is the mouse homologue of human gp-340, a glycoprotein that agglutinates microorganisms and binds the lung mucosal collectin surfactant protein-D (SP-D). Here we report that purified CRP-ductin binds human SP-D in a calcium-dependent manner and that the binding is not inhibited by maltose. The same properties have previously been observed for gp-340 binding of SP-D. CRP-ductin also showed calcium-dependent binding to both gram-positive and -negative bacteria. A polyclonal antibody raised against gp-340 reacted specifically with CRP-ductin in Western blots. Immunoreactivity to CRP-ductin was found in the exocrine pancreas, in epithelial cells throughout the gastrointestinal tract and in the parotid ducts. A panel of RNA preparations from mouse tissues was screened for CRP-ductin and SP-D expression by reverse transcription-PCR. The pancreas was the main site of synthesis of CRP-ductin, but transcripts were also readily amplified from salivary gland, the gastrointestinal tract, liver, testis, uterus and lung. Lung was the main site of synthesis of SP-D, but transcripts were also amplified from uterus, salivary gland, thymus, thyroid gland, pancreas and testis. We conclude that CRP-ductin is the mouse homologue of human gp-340 and that its capacity to bind SP-D as well as gramnegative and gram-positive bacteria suggests a role in mucosal immune defense.

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Section: Discussionmentioning

confidence: 98%

CRP‐ductin, the mouse homologue of gp‐340/deleted in malignant brain tumors 1 (DMBT1), binds gram‐positive and gram‐negative bacteria and interacts with lung surfactant protein D

et al. 2003

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“…Filtration of saliva prior to testing resulted in a partial decrease in HIV-1 inhibitory activity, indicating that saliva contains both filterable and nonfilterable antiviral factors (64). The filterable component was shown to be high-molecular-mass mucins, such as MG2 (150 to 200 kDa), which act by aggregating the virus, thus reducing titers of HIV-1 in saliva (24,30,57). Nagashunmugam et al (30) also demonstrated virus aggregation and stripping of the envelope glycoprotein gp120 from the virus by inhibitory components in sm/sl 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

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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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“…Peptides 7-9 were relatively less abundant in the AF SALSA compared with intestinal SALSA, whereas peptides 10 and 25 were relatively more abundant. It has long been known that SALSA binds to and agglutinates several types of bacteria in the mouth and in the gut (16)(17)(18)(19)(20)(21). The broad bacterial binding property has been assigned to one particular peptide sequence found in the SRCR domains (RVEVLYxxxSW) (21).…”

Section: Discussionmentioning

confidence: 99%

“…The immune functions of SALSA are apparent through its well-established ability to bind and agglutinate a broad spectrum of both Gram-negative and Gram-positive bacteria, as well as viruses (16)(17)(18)(19)(20)(21)(22). In several cases, such as with Salmonella enterica, Streptococcus mutans, HIV-1, and influenza A virus, SALSA has been shown to have a direct effect on controlling the infection (16,18,23,24). SALSA's antimicrobial effects are mediated in concert with other innate immune molecules such as mucin 5B, IgA, and surfactant proteins A and D, all of which act as endogenous ligands for SALSA (7,(25)(26)(27).…”

mentioning

confidence: 99%

The Salivary Scavenger and Agglutinin in Early Life: Diverse Roles in Amniotic Fluid and in the Infant Intestine

Reichhardt

Jarva

Been

et al. 2014

The Journal of Immunology

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The salivary scavenger and agglutinin (SALSA), also known as gp340 and dmbt1, is an antimicrobial and inflammation-regulating molecule located at the mucosal surfaces. The present study revealed that SALSA was present in the amniotic fluid (AF) and exceptionally enriched in both meconium and feces of infants. Based on immunological and mass spectrometric analysis, SALSA was estimated to constitute up to 4–10% of the total protein amount in meconium, making it one of the most abundant proteins. SALSA proteins in the AF and intestinal samples were polymorphic and exhibited varying polypeptide compositions. In particular, a different abundance of peptides corresponding to functionally important structures was found in the AF and intestinal SALSA. The AF form of SALSA had a more intact structure and contained peptides from the zona pellucida domain, which is involved in cell differentiation and oligomerization. In contrast, the intestinal SALSA was more enriched with the scavenger receptor cysteine-rich domains. The AF, but not the meconium SALSA, bound to Streptococcus pyogenes, S. agalactiae, S. gordonii, and Escherichia coli. Furthermore, differential binding was observed also to known endogenous ligands C1q, mannose-binding lectin, and secretory IgA. Our results have thus identified mucosal body compartments, where SALSA is particularly abundant, and suggest that SALSA exhibits varying functions in the different mucosal locations. The high levels of SALSA in AF and the infant intestine suggest a robust and important function for SALSA during the fetal development and in the mucosal innate immune defense of infants.

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Human Submandibular Saliva Inhibits Human Immunodeficiency Virus Type 1 Infection by Displacing Envelope Glycoprotein gp120 from the Virus

Cited by 61 publications

References 33 publications

CRP‐ductin, the mouse homologue of gp‐340/deleted in malignant brain tumors 1 (DMBT1), binds gram‐positive and gram‐negative bacteria and interacts with lung surfactant protein D

CRP‐ductin, the mouse homologue of gp‐340/deleted in malignant brain tumors 1 (DMBT1), binds gram‐positive and gram‐negative bacteria and interacts with lung surfactant protein D

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

The Salivary Scavenger and Agglutinin in Early Life: Diverse Roles in Amniotic Fluid and in the Infant Intestine

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