Mother-to-Child HIV-1 Transmission Events Are Differentially Impacted by Breast Milk and Its Components from HIV-1-Infected Women

Breast milk is a vehicle of infection and source of protection in post-natal mother-to-child HIV-1 transmission (MTCT). Understanding the mechanism by which breast milk limits vertical transmission will provide critical insight into the design of preventive and therapeutic approaches to interrupt HIV-1 mucosal transmission. However, characterization of the inhibitory activity of breast milk in human intestinal mucosa, the portal of entry in postnatal MTCT, has been constrained by the limited availability of primary mucosal target cells and tissues to recapitulate mucosal transmission ex vivo. 

Here, we characterized the impact of skimmed breast milk, breast milk antibodies (Igs) and non-Ig components from HIV-1-infected Ugandan women on the major events of HIV-1 mucosal transmission using primary human intestinal cells and tissues. HIV-1-specific IgG antibodies and non-Ig components in breast milk inhibited the uptake of Ugandan HIV-1 isolates by primary human intestinal epithelial cells, viral replication in and transport of HIV-1- bearing dendritic cells through the human intestinal mucosa. 

Breast milk HIV-1-specific IgG and IgA, as well as innate factors, blocked the uptake and transport of HIV-1 through intestinal mucosa. Thus, breast milk components have distinct and complementary effects in reducing HIV-1 uptake, transport through and replication in the intestinal mucosa and, therefore, likely contribute to preventing postnatal HIV-1 transmission. 

Our data suggests that a successful preventive or therapeutic approach would require multiple immune factors acting at multiple steps in the HIV-1 mucosal transmission process.

Below:  Inhibition of HIV-1 uptake by primary human intestinal epithelial cells (IECs). (A) Breast milk inhibition of subtype A and D HIV-1 uptake by IECs. (B) Dose-dependent breast milk inhibition of IEC uptake of subtype A HIV-1 by breast milk from an HIV-1-infected Ugandan woman. Ugandan subtype A or D viruses were pre-incubated with breast milk from an HIV-1-infected Ugandan woman for 30 min and then incubated with isolated primary IECs for 2 hr. The uptake of virus by IECs was measured by p24 ELISA with the uptake of virus pre-incubated with media defined as 100%, i.e. no inhibition. The range of p24 in samples treated with breast milk was 622–1300 pg/mL. Results are the mean values ±SD using IECs isolated from 4 separate tissue donors. Differences in IEC uptake of virus pre-incubated with breast milk and virus pre-incubated with media was determined by non-parametric Mann-Whitney test with significance indicated by * (p < 0.05).

Full article at:   http://goo.gl/LlKwwd

By:   Shen R1, Achenbach J2, Shen Y3, Palaia J2, Rahkola JT2,4, Nick HJ1, Smythies LE1, McConnell M5, Fowler MG6, Smith PD1,7, Janoff EN2,4.

• 1Department of Medicine (Division of Gastroenterology), University of Alabama at Birmingham, Birmingham, Alabama, United States of America.
• 2Mucosal and Vaccine Research Program Colorado (MAVRC), University of Colorado Denver, Aurora, Colorado, United States of America.
• 3Department of Biological Sciences, Auburn University, Auburn, Alabama United States of America.
• 4Denver Veterans Affairs Medical Center, Denver, Colorado, United States of America.
• 5Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
• 6The Makerere University-Johns Hopkins University Research Collaboration, Kampala, Uganda.
• 7Veterans Affairs Medical Center, Birmingham, Alabama, United States of America. 

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