title: MxB binds to the HIV-1 core and prevents the uncoating process of HIV-1.
abstract: BACKGROUND
  The IFN-α-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.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fricke
authors.forename: Tommy E
authors.initials: TE
authors.lastname: White
authors.forename: Bianca
authors.initials: B
authors.lastname: Schulte
authors.forename: Daniel A
authors.initials: DA
authors.lastname: de Souza Aranha Vieira
authors.forename: Adarsh
authors.initials: A
authors.lastname: Dharan
authors.forename: Edward M
authors.initials: EM
authors.lastname: Campbell
authors.forename: Alberto
authors.initials: A
authors.lastname: Brandariz-Nuñez
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx 10461, NY, USA. Felipe.Diaz-Griffero@einstein.yu.edu.
authors.forename: Felipe
authors.initials: F
authors.lastname: Diaz-Griffero
mesh_terms: D002213:Capsid / Q000378:metabolism; D045744:Cell Line, Tumor; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology*; D015497:HIV-1 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D064547:Myxovirus Resistance Proteins / Q000378:metabolism*; D011485:Protein Binding; D020298:U937 Cells; D014758:Viral Core Proteins / Q000378:metabolism*
chemical_list: C579068:MX2 protein, human; D064547:Myxovirus Resistance Proteins; D014758:Viral Core Proteins