The role of crude human saliva and purified salivary MUC5B and MUC7 mucins in the inhibition of Human Immunodeficiency Virus type 1 in an inhibition assay

Habte, Habtom H.; Mall, Anwar Suleman; Beer, Corena de; Lotz, Zoë; Kahn, Delawir

doi:10.1186/1743-422x-3-99

Cited by 60 publications

(67 citation statements)

References 40 publications

(56 reference statements)

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“…Our laboratory showed that human saliva and its purified mucin from uninfected individuals inhibit HIV-1 in an in vitro assay [10], whilst mucins from HIV-positive patients did not [11]. We also showed that crude virus-free breast milk did not inhibit the virus, while purified mucin did [12].…”

Section: Introductionmentioning

confidence: 71%

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Purified Human Breast Milk MUC1 and MUC4 Inhibit Human Immunodeficiency Virus

Mthembu

Lotz²,

Tyler

et al. 2014

Neonatology

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Background: The HIV-AIDS pandemic is prevalent in sub-Saharan Africa. Breastfeeding is a risk factor, with transmission from mother to child being as high as 40%. Objectives: To determine the antiviral activity of crude breast milk and its purified mucins MUC1 and MUC4 against HIV-1 in patients who were HIV positive compared to those who were not. Methods: Twenty-one human milk samples were taken from both groups. Breast milk mucins were purified by density-gradient ultracentrifugation in caesium chloride and analyzed by SDS-PAGE, Western blotting and amino acid content. The inhibition of the virus by crude milk and purified mucin was assayed by an in vitro HIV-1 p24 assay. Results: SDS-PAGE for purified mucin showed several high-molecular-weight bands for the HIV-negative group and prominently stained single bands on the stacking gel with faintly periodic acid Schiff-positive glycoprotein bands observed in some cases in the running gel for the HIV-positive mucins. Western blot analysis identified the mucins in both groups to be MUC1 and MUC4. Both mucins showed more intensity on Western blotting for the HIV-positive group. There was no difference in the content of serine, threonine and proline of purified mucins for both groups. HIV-1 was not inhibited by crude breast milk from normal (13/14 samples) and infected individuals (19/19 samples). Fifteen of 20 and 16/18 samples of purified mucin from the uninfected and HIV-positive groups, respectively, inhibited the virus. Conclusions: Crude breast milk does not inhibit HIV-1, whilst purified mucins do in an in vitro assay.

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Section: Introductionmentioning

confidence: 71%

“…The idea of investigating the role of breast milk and its mucin constituents in the inhibition of HIV-1 arose after our laboratory showed that saliva and its mucins inhibited the virus in an in vitro assay [10]. …”

Section: Discussionmentioning

confidence: 99%

Purified Human Breast Milk MUC1 and MUC4 Inhibit Human Immunodeficiency Virus

Mthembu

Lotz²,

Tyler

et al. 2014

Neonatology

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“…As in the case of the MUC5B and MUC7 from HIV negative individuals [4], serial tenfold dilution, (10 -1 to 10 -4 ) of the MUC5B and MUC7 mucins, starting at 0.9 mg mucin, from HIV patients of all the different CD4 counts (< 200, 200-400 and > 400) were done in triplicate and this made no difference to infectivity (data not shown).…”

Section: Resultsmentioning

confidence: 94%

“…We hypothesized and confirmed that salivary MUC5B and MUC7 [4], breast milk mucin (MUC1) [5] and cervical or pregnancy plug mucins [6] inhibited HIV-1 activity in an in vitro inhibition assay. We have also shown the inhibition of poxvirus activity by MUC1 [7].…”

Section: Introductionmentioning

confidence: 82%

Anti-HIV-1 activity of salivary MUC5B and MUC7 mucins from HIV patients with different CD4 counts

Habte

Beer

Lotz

et al. 2010

Virol J

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BackgroundWe have previously shown that MUC5B and MUC7 mucins from saliva of HIV negative individuals inhibit HIV-1 activity by 100% in an in vitro assay. The purpose of this subsequent study was to investigate whether MUC5B and MUC7 from saliva of HIV patients or with full blown AIDS had a similar inhibitory activity against the virus.MethodsSalivary MUC5B and MUC7 from HIV patients with different CD4 counts (< 200, 200-400 and > 400) were incubated with HIV-1 prior to infection of the human T lymphoblastoid cell line (CEM SS cells). Cells were then cultured and viral replication was measured by a qualitative p24 antigen assay. The size, charge and immunoreactivity of mucins from HIV negative and positive individuals was also analysed by SDS-PAGE, Western blot and ELISA respectively.ResultsIt was shown that irrespective of their CD4 counts both MUC5B and MUC7 from HIV patients, unlike the MUC5B and MUC7 from HIV negative individuals, did not inhibit HIV-1 activity. Size, charge and immunoreactivity differences between the mucins from HIV negative and positive individuals and among the mucins from HIV patients of different CD4 count was observed by SDS-PAGE, Western blot and ELISA.ConclusionsPurified salivary mucins from HIV positive patients do not inhibit the AIDS virus in an in vitro assay. Although the reason for the inability of mucins from infected individuals to inhibit the virus is not known, it is likely that there is an alteration of the glycosylation pattern, and therefore of charge of mucin, in HIV positive patients. The ability to inhibit the virus by aggregation by sugar chains is thus diminished.

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“…Defects in mucin production can lead to diseases such as ulcerative colitis when mucins are underproduced or cystic fibrosis and asthma when mucins are overproduced (4)(5)(6). In addition, studies have shown that mucins can interact with microbes, such as Helicobacter pylori, Haemophilus parainfluenzae, and human immunodeficiency virus (7)(8)(9)(10). These diseases and microbial interactions highlight the necessity of mucins as one of the body's key natural defenses; however, few studies have focused specifically on the connection between MUC5B salivary mucins and oral diseases.…”

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Salivary Mucins Protect Surfaces from Colonization by Cariogenic Bacteria

Frenkel

Ribbeck

2015

Appl Environ Microbiol

107

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bUnderstanding how the body's natural defenses function to protect the oral cavity from the myriad of bacteria that colonize its surfaces is an ongoing topic of research that can lead to breakthroughs in treatment and prevention. One key defense mechanism on all moist epithelial linings, such as the mouth, gastrointestinal tract, and lungs, is a layer of thick, well-hydrated mucus. The main gel-forming components of mucus are mucins, large glycoproteins that play a key role in host defense. This study focuses on elucidating the connection between MUC5B salivary mucins and dental caries, one of the most common oral diseases. Dental caries is predominantly caused by Streptococcus mutans attachment and biofilm formation on the tooth surface. Once S. mutans attaches to the tooth, it produces organic acids as metabolic by-products that dissolve tooth enamel, leading to cavity formation. We utilize CFU counts and fluorescence microscopy to quantitatively show that S. mutans attachment and biofilm formation are most robust in the presence of sucrose and that aqueous solutions of purified human MUC5B protect surfaces by acting as an antibiofouling agent in the presence of sucrose. In addition, we find that MUC5B does not alter S. mutans growth and decreases surface attachment and biofilm formation by maintaining S. mutans in the planktonic form. These insights point to the importance of salivary mucins in oral health and lead to a better understanding of how MUC5B could play a role in cavity prevention or diagnosis. One of the body's key defense mechanisms on wet epithelial linings, such as the mouth, gastrointestinal tract, and lungs, is a layer of thick, well-hydrated mucus. The viscoelastic properties of mucus are attributed to mucins, large glycoproteins that play a key role in host defense and maintaining a healthy microbial environment (1-3). Defects in mucin production can lead to diseases such as ulcerative colitis when mucins are underproduced or cystic fibrosis and asthma when mucins are overproduced (4-6). In addition, studies have shown that mucins can interact with microbes, such as Helicobacter pylori, Haemophilus parainfluenzae, and human immunodeficiency virus (7-10). These diseases and microbial interactions highlight the necessity of mucins as one of the body's key natural defenses; however, few studies have focused specifically on the connection between MUC5B salivary mucins and oral diseases. This study fills this gap in understanding by exploring the connection between purified human MUC5B and the virulence of Streptococcus mutans, one of the main cavitycausing bacteria naturally found in the oral cavity (11). MUC7 is another salivary mucin, but MUC5B is the primary mucin component of the dental pellicle coating the soft and hard tissues in the oral cavity (12, 13). Importantly, the effects of MUC5B are characterized in a clinically relevant three-dimensional model that mimics the natural environment in the oral cavity; mucins are secreted into an aqueous phase as opposed to a two-dimensional surfac...

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The role of crude human saliva and purified salivary MUC5B and MUC7 mucins in the inhibition of Human Immunodeficiency Virus type 1 in an inhibition assay

Cited by 60 publications

References 40 publications

Purified Human Breast Milk MUC1 and MUC4 Inhibit Human Immunodeficiency Virus

Purified Human Breast Milk MUC1 and MUC4 Inhibit Human Immunodeficiency Virus

Anti-HIV-1 activity of salivary MUC5B and MUC7 mucins from HIV patients with different CD4 counts

Salivary Mucins Protect Surfaces from Colonization by Cariogenic Bacteria

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