Determinants of Tenascin-C and HIV-1 envelope binding and neutralization.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Mangan, RJ; Stamper, L; Ohashi, T; Eudailey, JA; Go, EP; Jaeger, FH; Itell, HL; Watts, BE; Fouda, GG; Erickson, HP; Alam, SM; Desaire, H; Permar, SR

Published Date

  • July 2019

Published In

Volume / Issue

  • 12 / 4

Start / End Page

  • 1004 - 1012

PubMed ID

  • 30976088

Pubmed Central ID

  • 30976088

Electronic International Standard Serial Number (EISSN)

  • 1935-3456

Digital Object Identifier (DOI)

  • 10.1038/s41385-019-0164-2

Language

  • eng

Conference Location

  • United States