title: The Presence and Anti-HIV-1 Function of Tenascin C in Breast Milk and Genital Fluids.
abstract: Tenascin-C (TNC) is a newly identified innate HIV-1-neutralizing protein present in breast milk, yet its presence and potential HIV-inhibitory function in other mucosal fluids is unknown. In this study, we identified TNC as a component of semen and cervical fluid of HIV-1-infected and uninfected individuals, although it is present at a significantly lower concentration and frequency compared to that of colostrum and mature breast milk, potentially due to genital fluid protease degradation. However, TNC was able to neutralize HIV-1 after exposure to low pH, suggesting that TNC could be active at low pH in the vaginal compartment. As mucosal fluids are complex and contain a number of proteins known to interact with the HIV-1 envelope, we further studied the relationship between the concentration of TNC and neutralizing activity in breast milk. The amount of TNC correlated only weakly with the overall innate HIV-1-neutralizing activity of breast milk of uninfected women and negatively correlated with neutralizing activity in milk of HIV-1 infected women, indicating that the amount of TNC in mucosal fluids is not adequate to impede HIV-1 transmission. Moreover, the presence of polyclonal IgG from milk of HIV-1 infected women, but not other HIV-1 envelope-binding milk proteins or monoclonal antibodies, blocked the neutralizing activity of TNC. Finally, as exogenous administration of TNC would be necessary for it to mediate measurable HIV-1 neutralizing activity in mucosal compartments, we established that recombinantly produced TNC has neutralizing activity against transmitted/founder HIV-1 strains that mimic that of purified TNC. Thus, we conclude that endogenous TNC concentration in mucosal fluids is likely inadequate to block HIV-1 transmission to uninfected individuals.
authors.affiliation: Duke Human Vaccine Institute, Duke University, Durham, North Carolina, United States of America.
authors.forename: Robin G
authors.initials: RG
authors.lastname: Mansour
authors.affiliation: Duke Human Vaccine Institute, Duke University, Durham, North Carolina, United States of America.
authors.forename: Lisa
authors.initials: L
authors.lastname: Stamper
authors.affiliation: Duke Human Vaccine Institute, Duke University, Durham, North Carolina, United States of America.
authors.forename: Frederick
authors.initials: F
authors.lastname: Jaeger
authors.affiliation: Duke Human Vaccine Institute, Duke University, Durham, North Carolina, United States of America.
authors.forename: Erin
authors.initials: E
authors.lastname: McGuire
authors.affiliation: Duke Human Vaccine Institute, Duke University, Durham, North Carolina, United States of America.
authors.forename: Genevieve
authors.initials: G
authors.lastname: Fouda
authors.affiliation: Duke Human Vaccine Institute, Duke University, Durham, North Carolina, United States of America.
authors.forename: Joshua
authors.initials: J
authors.lastname: Amos
authors.affiliation: Lactation Support Program, Boston Children's Hospital, Boston, Massachusetts, United States of America.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Barbas
authors.affiliation: Department of Cell Biology, Duke University, Durham, North Carolina, United States of America.
authors.forename: Tomoo
authors.initials: T
authors.lastname: Ohashi
authors.affiliation: Duke Human Vaccine Institute, Duke University, Durham, North Carolina, United States of America.
authors.forename: S Munir
authors.initials: SM
authors.lastname: Alam
authors.affiliation: Department of Cell Biology, Duke University, Durham, North Carolina, United States of America.
authors.forename: Harold
authors.initials: H
authors.lastname: Erickson
authors.affiliation: Duke Human Vaccine Institute, Duke University, Durham, North Carolina, United States of America.|Department of Pediatrics, Duke University, Durham, North Carolina, United States of America.
authors.forename: Sallie R
authors.initials: SR
authors.lastname: Permar
mesh_terms: D057134:Antibodies, Neutralizing / Q000276:immunology; D002584:Cervix Uteri / Q000276:immunology; D045604:Extracellular Fluid / Q000276:immunology*; D005260:Female; D005835:Genitalia; D015483:HIV Antibodies / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000378:metabolism; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007113:Immunity, Innate; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008894:Milk Proteins / Q000276:immunology* / Q000494:pharmacology; D008895:Milk, Human / Q000276:immunology*; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins; D012661:Semen / Q000276:immunology; D019063:Tenascin / Q000276:immunology* / Q000494:pharmacology
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D007074:Immunoglobulin G; D008894:Milk Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D019063:Tenascin