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

Retrovirology

Felipe Diaz-Griffero²  Alberto Brandariz-Nuñez¹  Edward M Campbell³  Adarsh Dharan³  Daniel A de Souza Aranha Vieira¹  Bianca Schulte¹  Tommy E White¹  Thomas Fricke¹ 

[1] Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx 10461, NY, USA;Albert Einstein College of Medicine, 1301 Morris Park – Price Center 501, Bronx 10461, NY, USA;Department of Microbiology and Immunology, Loyola University, Chicago 60153, IL, USA

关键词: Oligomerization;    Binding;    IFN-α;    Core;    Capsid;    Uncoating;    HIV-1;    MxB;   

Others  :  1159831
DOI  :  10.1186/s12977-014-0068-x

 received in 2014-07-25, accepted in 2014-07-30,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Fricke et al.; licensee BioMed Central Ltd.

【 图 表 】

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