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Tenascin-C is an innate broad-spectrum, HIV-1-neutralizing protein in breast milk.

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Date
2013-11
Authors
Fouda, Genevieve G
Jaeger, Frederick H
Amos, Joshua D
Ho, Carrie
Kunz, Erika L
Anasti, Kara
Stamper, Lisa W
Liebl, Brooke E
Barbas, Kimberly H
Ohashi, Tomoo
Moseley, Martin Arthur
Liao, Hua-Xin
Erickson, Harold P
Alam, S Munir
Permar, Sallie R
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(15 total)
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Abstract
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.
Type
Journal article
Subject
Cell Line
Milk, Human
Humans
HIV-1
Acquired Immunodeficiency Syndrome
Tenascin
Viral Envelope Proteins
Blotting, Western
Chromatography, Ion Exchange
Immunoprecipitation
Inhibitory Concentration 50
Dose-Response Relationship, Drug
Female
Mass Spectrometry
Infectious Disease Transmission, Vertical
Permalink
https://hdl.handle.net/10161/16467
Published Version (Please cite this version)
10.1073/pnas.1307336110
Publication Info
Fouda, Genevieve G; Jaeger, Frederick H; Amos, Joshua D; Ho, Carrie; Kunz, Erika L; Anasti, Kara; ... Permar, Sallie R (2013). Tenascin-C is an innate broad-spectrum, HIV-1-neutralizing protein in breast milk. Proceedings of the National Academy of Sciences of the United States of America, 110(45). 10.1073/pnas.1307336110. Retrieved from https://hdl.handle.net/10161/16467.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Alam

S. Munir Alam

Professor in Medicine
Research Interests.  The Alam laboratory’s primary research is focused on understanding the biophysical properties of antigen-antibody binding and the molecular events of early B cell activation using the HIV-1 broadly neutralizing antibody (bnAb) lineage models. We are studying how HIV-1 Envelope proteins of varying affinities are sensed by B cells expressing HIV-1 bnAbs or their germline antigen receptors and initiate early signaling events for their activation. In the lon
Erickson

Harold Paul Erickson

James B. Duke Distinguished Professor of Cell Biology
Cytoskeleton: It is now clear that the actin and microtubule cytoskeleton originated in bacteria. Our major research is on FtsZ, the bacterial tubulin homolog, which assembles into a contractile ring that divides the bacterium. We have studied FtsZ assembly in vitro, and found that it assembles into thin protofilaments (pfs). Dozens of these pfs are further clustered to form the contractile Z-ring in vivo. Some important discoveries in the last ten years include: &bul
Fouda

Genevieve Giny Fouda

Associate Professor in Pediatrics
Dr Fouda's research interest is in understanding infant immune responses in the setting of infection and vaccination. Her current work focuses on HIV mother to child transmission.
Liao

Hua-Xin Liao

Adjunct Professor in the Department of Medicine
Dr. Liao is a Professor of Medicine and Research Director of Duke Human Vaccine Institute. Dr. Liao is a MD virologistt rained in China. In early 1980’s, Dr. Liao made major contributions to the first isolation of epidemic hemorrhagic fever virus (hataanvirus) from Apodemus agraius using tissue culture in China. The successful identification and isolation of Hataanvirus enabled the early diagnosis and treatment of the disease, and advancement of HFRS research towards prevention by de
Moseley

Martin Arthur Moseley III

Adjunct Professor in the Department of Cell Biology

Tomoo Ohashi

Assistant Research Professor of Cell Biology
Permar

Sallie Robey Permar

Wilburt C. Davison Distinguished Professor
Dr. Permar's work focuses on the development of vaccines to prevent vertical transmission of neonatal viral pathogens. She has utilized the nonhuman primate model of HIV/AIDS to characterize the virus-specific immune responses and virus evolution in breast milk and develop a maternal vaccine regimen for protection against breast milk transmission of HIV. In addition, Dr. Permar's lab has advanced the understanding of HIV-specific immune responses and virus evolution in vertically-transmitting an
This author no longer has a Scholars@Duke profile, so the information shown here reflects their Duke status at the time this item was deposited.
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