Infective and anti-infective properties of breastmilk from HIV-1-infected women

Perre, Philippe Van de; Simonon, Arlette; Karita, Etienne; Butera, J.; Hitimana, D.G.; Mukamabano, B.; Goethem, C. Van; Lepage, Philippe; Dabis, François; Msellati, Philippe

doi:10.1016/0140-6736(93)91210-d

Cited by 210 publications

(68 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[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][13][14] suggesting a role for these mucosal responses in resistance to HIV.…”

mentioning

confidence: 88%

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

View full text Add to dashboard Cite

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...

show abstract

mentioning

confidence: 88%

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

View full text Add to dashboard Cite

show abstract

“…Our data are similar to those reported in cohorts of heterosexual transmission, where the likelihood of transmission of multiple variants is around 20%, and overall suggest that the low probability of transmission for any given exposure generally results in the transmission of a single variant when an infection does occur. 12,[28][29][30][31][32][33][34] We next compared the number of putative N-linked glycosylation sites (N-glycosite program, hiv.lanl.gov) and sequence length between mother and infant viral populations. Fewer glycosylation sites and shorter full-length env sequences were seen in infants compared to their mothers over env in all three transmission pairs (Supplementary Table S1).…”

mentioning

confidence: 99%

Short Communication: HIV Type 1 Subtype C Variants Transmitted Through the Bottleneck of Breastfeeding Are Sensitive to New Generation Broadly Neutralizing Antibodies Directed Against Quaternary and CD4-Binding Site Epitopes

Russell

Ojeda

Fouda

et al. 2013

AIDS Research and Human Retroviruses

View full text Add to dashboard Cite

Mother-to-child transmission of HIV-1 subtype C can occur in utero, intrapartum, or via breast milk exposure. While not well understood, there are putative differences in the mechanisms involved with the distinct routes of vertical HIV transmission. Here, we address the question of whether specific viral characteristics are common to variants transmitted through breastfeeding that may facilitate evasion of innate or adaptive immune responses. We amplified the envelope gene (env) from the plasma of six infants during acute infection who were infected with HIV-1 subtype C through breastfeeding, and from three available matched maternal samples. We sequenced the full-length env genes in these subjects revealing heterogeneous viral populations in the mothers and homogeneous populations in the infants. In five infants, the viral population arose from a single variant, while two variants were detected in the remaining infant. Infant env sequences had fewer N-linked glycosylation sites and shorter sequences than those of the available matched maternal samples. Though the small size of the study precluded our ability to test statistical significance, these results are consistent with selection for virus with shorter variable loops and fewer glycosylation sites during transmission of HIV-1 subtype C in other settings. Transmitted envs were resistant to neutralization by antibodies 2G12 and 2F5, but were generally sensitive to the more broadly neutralizing PG9, PG16, and VRC01, indicating that this new generation of broadly neutralizing monoclonal antibodies could be efficacious in passive immunization strategies.T ransmission of human immunodeficiency virus-1 (HIV-1) through breastfeeding (BF) makes up one-third to one-half of all mother-to-child transmission events.1 The mechanism(s) of transmission, however, are poorly understood. The oral cavity and gastrointestinal tract of breastfed infants are exposed daily to both cell-free and cell-associated HIV-1, 2-4 yet the majority of infants remain uninfected even if neither mother nor baby receive antiretroviral prophylaxis. 5This inefficiency of transmission indicates that anatomical, innate, and/or adaptive mechanisms of protection are able to prevent transmission to a great extent.6-11 Maternal antibodies could prevent infection either through direct binding of virus in the breast milk, or by their systemic and mucosal presence in the infant. This passive maternal immunity in the infant increases in concentration during the last trimester of gestation, and continues to pass into the infant through breastfeeding.Studies of in utero and intrapartum transmission have shown a universal bottleneck in genetic diversity from mother to child, as well as differences in the characteristics of transmitted virus for in utero versus intrapartum transmission. 12,13 Data are very limited for breastfeeding pairs, but one study of three breast milk transmission events found a similar bottleneck for HIV-1 subtype A.14 We previously demonstrated that the viral population found in ...

show abstract

“…[57][58][59] Breast milk-mediated MTCT of HIV-1 remains an enigma, so identifying the ability of breast milk components that promote or inhibit HIV-1 MTCT could help limit the occurrence of postpartum HIV-1 transmission. Human breast milk contains many antibacterial and antiviral compounds, and breast milk-derived exosomes have been shown to inhibit HIV-1 infection.…”

Section: Discussionmentioning

confidence: 99%

Role of TIM-4 in exosome-dependent entry of HIV-1 into human immune cells

Sims

Farrow

Williams

et al. 2017

IJN

View full text Add to dashboard Cite

Exosomes, 30–200 nm nanostructures secreted from donor cells and internalized by recipient cells, can play an important role in the cellular entry of some viruses. These microvesicles are actively secreted into various body fluids, including blood, urine, saliva, cerebrospinal fluid, and breast milk. We successfully isolated exosomes from human breast milk and plasma. The size and concentration of purified exosomes were measured by nanoparticle tracking, while Western blotting confirmed the presence of the exosomal-associated proteins CD9 and CD63, clathrin, and T cell immunoglobulin and mucin proteins (TIMs). Through viral infection assays, we determined that HIV-1 utilizes an exosome-dependent mechanism for entry into human immune cells. The virus contains high amounts of phosphatidylserine (PtdSer) and may bind PtdSer receptors, such as TIMs. This mechanism is supported by our findings that exosomes from multiple sources increased HIV-1 entry into T cells and macrophages, and viral entry was potently blocked with anti-TIM-4 antibodies.

show abstract

Infective and anti-infective properties of breastmilk from HIV-1-infected women

Cited by 210 publications

References 18 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

Short Communication: HIV Type 1 Subtype C Variants Transmitted Through the Bottleneck of Breastfeeding Are Sensitive to New Generation Broadly Neutralizing Antibodies Directed Against Quaternary and CD4-Binding Site Epitopes

Role of TIM-4 in exosome-dependent entry of HIV-1 into human immune cells

Contact Info

Product

Resources

About