- Authors: Mangan, R. J., Stamper, L., Ohashi, T., Eudailey, J. A., Go, E. P., Jaeger, F. H., Itell, H. L., Watts, B. E., Fouda, G. G., Erickson, H. P., Alam, S. M., Desaire, H., Permar, S. R.
- Year: 2019
- Journal: Mucosal Immunol 12 1004-1012
- Applications: in vitro / DNA / jetPRIME
- Cell types:
- Name: HEK-293T
Description: Human embryonic kidney Fibroblast
Known as: HEK293T, 293T
- Name: Lenti-X 293T
- Name: HEK-293T
Interactions between innate antiviral factors at mucosal surfaces and HIV-1 virions contribute to the natural inefficiency of HIV-1 transmission and are a platform to inform the development of vaccine and nonvaccine strategies to block mucosal HIV-1 transmission. Tenascin-C (TNC) is a large, hexameric extracellular matrix glycoprotein identified in breast milk and genital fluids that broadly neutralizes HIV-1 via interaction with the HIV-1 Envelope (Env) variable 3 (V3) loop. In this report, we characterize the specific determinants of the interaction between TNC and the HIV-1 Env. We observed that TNC binding and neutralization of HIV-1 is dependent on the TNC fibrinogen-like globe (fbg) and fibronectin-type III (fn) domains, oligomerization, and its newly-mapped glycan structure. Moreover, we observed that TNC-mediated neutralization is also dependent on Env V3 residues 321/322 and 326/327, which surround the IGDIR motif of the V3 loop, as well the N332 glycan, which is critical to the broadly neutralizing activity of glycan-dependent V3-specific antibodies such as PGT128. Our results demonstrate a striking parallel between innate and adaptive immune mechanisms of broad HIV neutralization and provide further insight into the host protein-virus interactions responsible for the natural inefficiency of mucosal HIV-1 transmission.