Antiviral Activity of Purified Human Breast Milk Mucin

Habte, Habtom H.; Kotwal, Girish J.; Lotz, Zoë; Tyler, Marilyn; Abrahams, Melissa-Rose; Rodriques, Jerry; Kahn, Delawir; Mall, Anwar Suleman

doi:10.1159/000100808

Cited by 47 publications

(31 citation statements)

References 42 publications

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“…The tolerance of VSV to MUC1 is a significant result. Although the role of MUC1 in oncolytic therapy has never been studied before, the O-linked carbohydrates of MUC1 purified from human breast milk can inhibit poxvirus (12), HIV (13,14), and rotavirus (15), and MUC1 expression can block adeno-associated virus attachment (16). Although VSV-⌬M51-GFP was slightly less infectious in MUC1-expressing KCM cells than in MUC1-null KCKO cells, the opposite could be seen in Panc02-based cell lines ( Fig.…”

Section: Discussionmentioning

confidence: 96%

“…MUC1 plays an important role in the development and progression of PDA and other cancers and is a major marker for poor prognosis (7)(8)(9)(10)(11). Importantly, while the role of MUC1 in vesicular stomatitis virus (VSV) infection or oncolytic virus (OV) therapy has never been studied before, the O-linked carbohydrates of MUC1 purified from human breast milk can inhibit poxvirus (12), HIV (13,14), and rotavirus (15), and MUC1 expression can block adeno-associated virus attachment (16).…”

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confidence: 99%

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Oncolytic Vesicular Stomatitis Virus in an Immunocompetent Model of MUC1-Positive or MUC1-Null Pancreatic Ductal Adenocarcinoma

Hastie

Besmer

Shah

et al. 2013

J Virol

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Vesicular stomatitis virus (VSV) is a promising oncolytic agent against various malignancies. Here, for the first time, we tested VSV in vitro and in vivo in a clinically relevant, immunocompetent mouse model of pancreatic ductal adenocarcinoma (PDA). Our system allows the study of virotherapy against PDA in the context of overexpression (80% of PDA patients) or no expression of human mucin 1 (MUC1), a major marker for poor prognosis in patients. In vitro, we tested three VSV recombinants, wildtype VSV, VSV-green fluorescent protein (VSV-GFP), and a safe oncolytic VSV-⌬M51-GFP, against five mouse PDA cell lines that either expressed human MUC1 or were MUC1 null. All viruses demonstrated significant oncolytic abilities independent of MUC1 expression, although VSV-⌬M51-GFP was somewhat less effective in two PDA cell lines. In vivo administration of VSV-⌬M51-GFP resulted in significant reduction of tumor growth for tested mouse PDA xenografts (؉MUC1 or MUC1 null), and antitumor efficacy was further improved when the virus was combined with the chemotherapeutic drug gemcitabine. The antitumor effect was transient in all tested groups. The developed system can be used to study therapies involving various oncolytic viruses and chemotherapeutics, with the goal of inducing tumor-specific immunity while preventing premature virus clearance.

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Section: Discussionmentioning

confidence: 96%

mentioning

confidence: 99%

Oncolytic Vesicular Stomatitis Virus in an Immunocompetent Model of MUC1-Positive or MUC1-Null Pancreatic Ductal Adenocarcinoma

Hastie

Besmer

Shah

et al. 2013

J Virol

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“…Although components, such as secretory IgA, lysozyme, lactoferrin, histatins, macrophages, and lymphocytes, are known to contribute to the local immunity of the milk, non-immunoglobulin components, such as mucin, also play a significant role in infant protection [18] . One example is the inhibition of rotavirus binding and infectivity by milk mucin [11] .…”

Section: Discussionmentioning

confidence: 99%

“…Purification and subsequent analysis of breast milk mucin was done according to the method described by Habte et al [18] . Briefly, mucin was prepared according to the method of Schroten et al [19] , semipurified by gel filtration on Sepharose CL-4B, and subsequently purified by caesium chloride isopycnic density gradient ultracentrifugation [20] .…”

Section: Mucin Preparation Purification Identification and Analysismentioning

confidence: 99%

Inhibition of Human Immunodeficiency Virus Type 1 Activity by Purified Human Breast Milk Mucin (MUC1) in an Inhibition Assay

et al. 2007

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It has been reported that breast-feeding is responsible for approximately 40% of the HIV transmissions from HIV-positive mothers to children. Human breast milk, however, is known to contain numerous biologically active components which protect breast-fed infants against bacteria, viruses, and toxins. The purpose of this study was to purify and characterize breast milk mucin and to determine its anti-HIV-1 activity in an HIV inhibition assay. Sepharose CL-4B column chromatography and caesium chloride isopycnic density gradient purification were used to isolate and purify the mucin. Following Western blotting and amino acid analysis, an HIV-1 inhibition assay was carried out to determine the anti-HIV-1 activity of crude breast milk and purified milk mucin (MUC1) by incubating them with HIV-1 prior to infection of the human T lymphoblastoid cell line (CEM SS cells). SDS-PAGE analysis of the mucin, together with its amino acid composition and Western blotting, suggested that this purified mucin from human breast milk was MUC1. The HIV inhibition assay revealed that while the purified milk mucin (MUC1) inhibited the HIV-1 activity by approximately 97%, there was no inhibition of the HIV-1 activity by crude breast milk. Although the reason for this is not clear, it is likely that because the MUC1 in crude milk is enclosed by fat globules, there may not be any physical contact between the mucin and the virus in the crude breast milk. Thus, there is a need to free the mucin from the fat globules for it to be effective against the virus.

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“…About 70% of mucins are present in the fat globule membrane (cream fractions) with the rest in skim milk [8]. Although human milk is rich in mucin [9], mother-to-child transmission of HIV-1 through breastfeeding accounts for the majority of HIV-1 infections among children.…”

Section: Introductionmentioning

confidence: 99%

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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Antiviral Activity of Purified Human Breast Milk Mucin

Cited by 47 publications

References 42 publications

Oncolytic Vesicular Stomatitis Virus in an Immunocompetent Model of MUC1-Positive or MUC1-Null Pancreatic Ductal Adenocarcinoma

Oncolytic Vesicular Stomatitis Virus in an Immunocompetent Model of MUC1-Positive or MUC1-Null Pancreatic Ductal Adenocarcinoma

Inhibition of Human Immunodeficiency Virus Type 1 Activity by Purified Human Breast Milk Mucin (MUC1) in an Inhibition Assay

Purified Human Breast Milk MUC1 and MUC4 Inhibit Human Immunodeficiency Virus

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