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

Abstract

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.

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

“…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.…”

“…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).…”

Purified Human Breast Milk MUC1 and MUC4 Inhibit Human Immunodeficiency Virus

“…We also showed that crude virus-free breast milk did not inhibit the virus, while purified mucin did [12]. …”

Tenascin-C is an innate broad-spectrum, HIV-1–neutralizing protein in breast milk

“…Moreover, it was recently established that milk of uninfected women abrogates oral HIV-1 transmission in humanized mice (10). Several antiviral glycoproteins contained in milk have been reported to inhibit HIV-1 replication, including lactoferrin (11,12), mucin-1 (13), and secretory leukocyte protease inhibitor (14,15). In addition, a recent study reported an association between the prevalence of certain oligosaccharides in milk and the risk of infant HIV-1 acquisition (16), potentially explained by the ability of oligosaccharides to prevent HIV-1 virion interaction with dendritic cells (17,18).…”