Tenascin-C is an innate broad-spectrum, HIV-1–neutralizing protein in breast milk
| العنوان: | Tenascin-C is an innate broad-spectrum, HIV-1–neutralizing protein in breast milk |
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| المؤلفون: | Harold P. Erickson, Erika L. Kunz, Kimberly H. Barbas, Hua-Xin Liao, Tomoo Ohashi, Genevieve G. Fouda, Lisa Stamper, Joshua D. Amos, Frederick H. Jaeger, S. Munir Alam, Brooke E. Liebl, M.A. Moseley, Sallie R. Permar, Kara Anasti, Carrie Ho |
| المصدر: | Proceedings of the National Academy of Sciences. 110:18220-18225 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Chemokine, medicine.drug_class, Blotting, Western, Tenascin, Breast milk, V3 loop, Monoclonal antibody, Mass Spectrometry, Virus, Cell Line, Inhibitory Concentration 50, Viral Envelope Proteins, medicine, Humans, Immunoprecipitation, Receptor, Acquired Immunodeficiency Syndrome, Multidisciplinary, Dose-Response Relationship, Drug, Milk, Human, biology, Tenascin C, virus diseases, Biological Sciences, Chromatography, Ion Exchange, Virology, Infectious Disease Transmission, Vertical, Immunology, HIV-1, biology.protein, Female |
| الوصف: | 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. |
| تدمد: | 1091-6490 0027-8424 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a9fa8dbd0552006e08afa12da3280b91 https://doi.org/10.1073/pnas.1307336110 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....a9fa8dbd0552006e08afa12da3280b91 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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