MxB binds to the HIV-1 core and prevents the uncoating process of HIV-1

Thomas Fricke, Tommy E. White, Bianca Schulte, Daniel A. de Souza Aranha Vieira, Adarsh Dharan, Edward M. Campbell, Alberto Brandariz-Nuñez, Felipe Diaz-Griffero

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

Background: The IFN-aα-inducible restriction factor MxB blocks HIV-1 infection after reverse transcription but prior to integration. Genetic evidence suggested that capsid is the viral determinant for restriction by MxB. This work explores the ability of MxB to bind to the HIV-1 core, and the role of capsid-binding in restriction. Results: We showed that MxB binds to the HIV-1 core and that this interaction leads to inhibition of the uncoating process of HIV-1. These results identify MxB as an endogenously expressed protein with the ability to inhibit HIV-1 uncoating. In addition, we found that a benzimidazole-based compound known to have a binding pocket on the surface of the HIV-1 capsid prevents the binding of MxB to capsid. The use of this small-molecule identified the MxB binding region on the surface of the HIV-1 core. Domain mapping experiments revealed the following requirements for restriction: 1) MxB binding to the HIV-1 capsid, which requires the 20 N-terminal amino acids, and 2) oligomerization of MxB, which is mediated by the C-terminal domain provides the avidity for the interaction of MxB with the HIV-1 core. Conclusions: Overall our work establishes that MxB binds to the HIV-1 core and inhibits the uncoating process of HIV-1. Moreover, we demonstrated that HIV-1 restriction by MxB requires capsid binding and oligomerization.

Original languageEnglish (US)
Article number68
JournalRetrovirology
Volume11
Issue number1
DOIs
StatePublished - Aug 14 2014

Keywords

  • Binding
  • Capsid
  • Core
  • HIV-1
  • IFN-aα
  • MxB
  • Oligomerization
  • Uncoating

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

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    Fricke, T., White, T. E., Schulte, B., de Souza Aranha Vieira, D. A., Dharan, A., Campbell, E. M., Brandariz-Nuñez, A., & Diaz-Griffero, F. (2014). MxB binds to the HIV-1 core and prevents the uncoating process of HIV-1. Retrovirology, 11(1), [68]. https://doi.org/10.1186/s12977-014-0068-x