The Presence and Anti-HIV-1 Function of Tenascin C in Breast Milk and Genital Fluids.
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 ind...
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Public Library of Science (PLoS)
2016-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0155261&type=printable |
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| author | Robin G Mansour Lisa Stamper Frederick Jaeger Erin McGuire Genevieve Fouda Joshua Amos Kimberly Barbas Tomoo Ohashi S Munir Alam Harold Erickson Sallie R Permar |
| author_facet | Robin G Mansour Lisa Stamper Frederick Jaeger Erin McGuire Genevieve Fouda Joshua Amos Kimberly Barbas Tomoo Ohashi S Munir Alam Harold Erickson Sallie R Permar |
| author_sort | Robin G Mansour |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0d138c83fe6941b59d080dbafb03f551 |
| institution | OA Journals |
| issn | 1932-6203 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-0d138c83fe6941b59d080dbafb03f5512025-08-20T02:15:42ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01115e015526110.1371/journal.pone.0155261The Presence and Anti-HIV-1 Function of Tenascin C in Breast Milk and Genital Fluids.Robin G MansourLisa StamperFrederick JaegerErin McGuireGenevieve FoudaJoshua AmosKimberly BarbasTomoo OhashiS Munir AlamHarold EricksonSallie R PermarTenascin-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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0155261&type=printable |
| spellingShingle | Robin G Mansour Lisa Stamper Frederick Jaeger Erin McGuire Genevieve Fouda Joshua Amos Kimberly Barbas Tomoo Ohashi S Munir Alam Harold Erickson Sallie R Permar The Presence and Anti-HIV-1 Function of Tenascin C in Breast Milk and Genital Fluids. PLoS ONE |
| title | The Presence and Anti-HIV-1 Function of Tenascin C in Breast Milk and Genital Fluids. |
| title_full | The Presence and Anti-HIV-1 Function of Tenascin C in Breast Milk and Genital Fluids. |
| title_fullStr | The Presence and Anti-HIV-1 Function of Tenascin C in Breast Milk and Genital Fluids. |
| title_full_unstemmed | The Presence and Anti-HIV-1 Function of Tenascin C in Breast Milk and Genital Fluids. |
| title_short | The Presence and Anti-HIV-1 Function of Tenascin C in Breast Milk and Genital Fluids. |
| title_sort | presence and anti hiv 1 function of tenascin c in breast milk and genital fluids |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0155261&type=printable |
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