A Human Milk Factor Inhibits Binding of Human Immunodeficiency Virus to the CD4 Receptor

Newburg, David S.; Viscidi, Raphael P.; Ruff, Andrea; Yolken, Robert H.

doi:10.1203/00006450-199201000-00004

Cited by 84 publications

(39 citation statements)

References 34 publications

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“…4 We previously observed associations between higher concentrations of alpha-defensins in breast milk and reduced HIV transmission. 35 Several experimental studies have described HIV inhibitory factors in breast milk, [36][37][38][39] yet clinical studies have not observed consistent correlations between concentrations of innate immune factors in breast milk, such as secretory leukocyte inhibitor (SLPI), lactoferrin, lysozyme, interleukin-8 and chemokines, and reduced vertical HIV transmission. [40][41][42] A specific oligosaccharide epitope in breast milk, Lewis X component, was recently discovered to be able to bind to dendritic cell-specific ICAM3-grabbing nonintegrin (DC-SIGN), thereby inhibiting HIV transfer to CD4 cells.…”

Section: Discussionmentioning

confidence: 99%

Hiv-specific secretory IgA in breast milk of HIV-positive mothers is not associated with protection against HIV transmission among breast-fed infants

Kuhn

Trabattoni

Kankasa

et al. 2006

The Journal of Pediatrics

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Objectives-To test whether secretory immunoglobulin A (sIgA) to human immunodeficiency virus (HIV) antigens in breast milk of HIV-positive women is associated with protection against HIV transmission among breast-fed infants.Study design-Nested, case-control design in which HIV-specific sIgA was measured in breast milk collected from 90 HIV-positive women enrolled in a study in Lusaka, Zambia. Milk samples were selected to include 26 HIV-positive mothers with infected infants (transmitters) and 64 mothers with uninfected infants (nontransmitters).Results-HIV-specific sIgA was detected more often in breast milk of transmitting mothers (76.9%) than in breast milk of nontransmitting mothers (46.9%, P = .009). There were no significant associations between HIV-specific sIgA in breast milk and other maternal factors, including HIV RNA quantities in breast milk, CD4 count, and plasma RNA quantities.Conclusions-HIV-specific sIgA in breast milk does not appear to be a protective factor against HIV transmission among breast-fed infants.Human immunodeficiency virus (HIV) can be transmitted from an HIV-infected mother to her child through breast-feeding. This poses a serious dilemma for health policy-makers. Although complete avoidance of breast-feeding would eliminate the risk of breast-feeding-associated transmission, breast milk substitutes are unaffordable, unavailable, unacceptable, and unsafe for many HIV-infected women in low resource settings. The quantity of viral RNA and cellassociated viral DNA in breast milk from HIV-positive women strongly predicts mother-tochild transmission among breast-fed infants. [1][2][3] What is puzzling, however, is why the majority of breast-fed infants born to HIV-positive mothers remain uninfected despite prolonged exposure. Although breast milk is clearly a route of transmission, human milk is also a rich source of a multitude of innate and specific immune factors that may play a role in modulating the risk of infection. 4 Better understanding of anti-infective properties of breast milk may assist Secretory immunoglobulin A (sIgA) is the predominant immunoglobulin in breast milk and is associated with passive immunity to other (non-HIV) pathogens among breast-fed infants. 5 HIV-specific IgA antibodies are detected in breast milk of a high proportion of HIV-positive, lactating women. [6][7][8] In an in vitro model, sIgA purified from colostrum was able to block one of the pathways involved in HIV penetration across mucosa, that is, transcytosis through epithelial cells, 9 suggesting that sIgA may be related to decreased infectivity of breast milk. Although persistence of HIV-specific IgA and IgM in breast milk was associated with reduced transmission in one study in Rwanda, 10 no protective association was observed in two other studies. 8,11 HIV-specific sIgA has been detected frequently in cervicovaginal samples from exposed but persistently uninfected cohorts of high-risk women, 12-14 suggesting a role for these mucosal responses in resistance to HIV. Purified sIgA from ex...

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Section: Discussionmentioning

confidence: 99%

Hiv-specific secretory IgA in breast milk of HIV-positive mothers is not associated with protection against HIV transmission among breast-fed infants

Kuhn

Trabattoni

Kankasa

et al. 2006

The Journal of Pediatrics

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“…In the case of all four virus strains, the inhibition was reduced or abolished by the chemical desialylation ofthe milk glycoprotein. The macromolecular fraction of human milk was further fractionated by high-resolution preparative isoelectric focusing ( 14). As depicted in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The recognition ofthe importance of rotaviral infections has led to a substantial effort directed at the prevention ofinfection by means ofactive immunization. However, current vaccine regimens have displayed variable degrees of efficacy, indicating the need for the better understanding of the mechanisms responsible for disease prevention (5,(13)(14)(15)(16)(17).…”

Section: Introductionmentioning

confidence: 99%

Human milk mucin inhibits rotavirus replication and prevents experimental gastroenteritis.

et al. 1992

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Acute gastrointestinal infections due to rotaviruses and other enteric pathogens are major causes of morbidity and mortality in infants and young children throughout the world. Breastfeeding can reduce the rate of serious gastroenteritis in infants; however, the degrees of protection offered against rotavirus infection vary in different populations. The mechanisms associated with milk-mediated protection against viral gastroenteritis have not been fully elucidated.We have isolated a macromolecular component of human milk that inhibits the replication of rotaviruses in tissue culture and prevents the development of gastroenteritis in an animal model system. Purification of the component indicates that the antiviral activity is associated with an acidic fraction (pI = 4.0-4.6), which is free of detectable immunoglobulins. Furthermore, high levels of antiviral activity are associated with an affinity-purified complex of human milk mucin. Deglycosylation of the mucin complex results in the loss of antiviral activity. Further purification indicated that rotavirus specifically binds to the milk mucin complex as well as to the 46-kD glycoprotein component ofthe complex. Binding to the 46-kD component was substantially reduced after chemical hydrolysis of sialic acid.We have documented that human milk mucin can bind to rotavirus and inhibit viral replication in vitro and in vivo. Variations in milk mucin glycoproteins may be associated with different levels of protection against infection with gastrointestinal pathogens. (J. Clin. Invest. 1992. 90:1984

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“…For example, milk proteins and derivates thereof show antifungal, antibacterial, and antiviral properties (7,8,13,19,39,44). Positively charged macromolecules can inhibit the binding of HIV-1 to the CD4 receptor (27,32), and negatively charged macromolecules can inhibit HIV-1 by binding to the positively charged V3 loop of gp120 (40). Most of these proteins need to be chemically modified in order to become inhibitory, but native lactoferrin (LF) inhibits HIV-1 replication in T cells (7,13).…”

Section: Human Immunodeficiency Virus Type 1 (Hiv-1) Infects Cd4mentioning

confidence: 99%

Lactoferrin Prevents Dendritic Cell-Mediated Human Immunodeficiency Virus Type 1 Transmission by Blocking the DC-SIGN—gp120 Interaction

Groot

Geijtenbeek²,

Sanders³

et al. 2005

J Virol

129

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One of the cell types first encountered by human immunodeficiency virus type 1 (HIV-1) following sexual transmission are dendritic cells (DC). DC capture HIV-1 through C-type lectin receptors, of which the best studied example is DC-SIGN, which mediates HIV-1 internalization. DC can keep the virus infectious for several days and are able to transmit HIV-1 to CD4؉ T cells. We tested proteins from milk and serum for their ability to block DC-mediated HIV-1 transmission, of which bovine lactoferrin (bLF) is the most potent inhibitor. bLF binds strongly to DC-SIGN, thus preventing virus capture and subsequent transmission. Interestingly, bLF is a much more efficient inhibitor of transmission than human lactoferrin. Since bLF is nontoxic and easy to purify in large quantities, it is an interesting candidate microbicide against HIV-1. Another advantage of bLF is its ability to block HIV-1 replication in T cells. DC-mediated capture of a bLF-resistant HIV-1 variant that was selected during long-term culturing in T cells could still be blocked by bLF. This underscores the usefulness of bLF as a microbicide drug to prevent HIV-1 transmission.

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A Human Milk Factor Inhibits Binding of Human Immunodeficiency Virus to the CD4 Receptor

Cited by 84 publications

References 34 publications

Hiv-specific secretory IgA in breast milk of HIV-positive mothers is not associated with protection against HIV transmission among breast-fed infants

Hiv-specific secretory IgA in breast milk of HIV-positive mothers is not associated with protection against HIV transmission among breast-fed infants

Human milk mucin inhibits rotavirus replication and prevents experimental gastroenteritis.

Lactoferrin Prevents Dendritic Cell-Mediated Human Immunodeficiency Virus Type 1 Transmission by Blocking the DC-SIGN—gp120 Interaction

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