| Autor: |
Fouda GG; Human Vaccine Institute, Department of Cell Biology, Institute for Genome Sciences and Policy, and Department of Pediatrics, Duke University Medical Center, Durham, NC 27710., Jaeger FH, Amos JD, Ho C, Kunz EL, Anasti K, Stamper LW, Liebl BE, Barbas KH, Ohashi T, Moseley MA, Liao HX, Erickson HP, Alam SM, Permar SR |
| Jazyk: |
angličtina |
| Zdroj: |
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2013 Nov 05; Vol. 110 (45), pp. 18220-5. Date of Electronic Publication: 2013 Oct 21. |
| DOI: |
10.1073/pnas.1307336110 |
| Abstrakt: |
Achieving an AIDS-free generation will require elimination of postnatal transmission of HIV-1 while maintaining the nutritional and immunologic benefits of breastfeeding for infants in developing regions. Maternal/infant antiretroviral prophylaxis can reduce postnatal HIV-1 transmission, yet toxicities and the development of drug-resistant viral strains may limit the effectiveness of this strategy. Interestingly, in the absence of antiretroviral prophylaxis, greater than 90% of infants exposed to HIV-1 via breastfeeding remain uninfected, despite daily mucosal exposure to the virus for up to 2 y. Moreover, milk of uninfected women inherently neutralizes HIV-1 and prevents virus transmission in animal models, yet the factor(s) responsible for this anti-HIV activity is not well-defined. In this report, we identify a primary HIV-1-neutralizing protein in breast milk, Tenascin-C (TNC). TNC is an extracellular matrix protein important in fetal development and wound healing, yet its antimicrobial properties have not previously been established. Purified TNC captured and neutralized multiclade chronic and transmitted/founder HIV-1 variants, and depletion of TNC abolished the HIV-1-neutralizing activity of milk. TNC bound the HIV-1 Envelope protein at a site that is induced upon engagement of its primary receptor, CD4, and is blocked by V3 loop- (19B and F39F) and chemokine coreceptor binding site-directed (17B) monoclonal antibodies. Our results demonstrate the ability of an innate mucosal host protein found in milk to neutralize HIV-1 via binding to the chemokine coreceptor site, potentially explaining why the majority of HIV-1-exposed breastfed infants are protected against mucosal HIV-1 transmission. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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