HIV-1 Vif: Targeting its molecular interactions

Univ Of Massachusetts Med Sch Worcester, Worcester MA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): The structure and functional interactions of HIV-1 Vif are still unknown in molecular and atomic detail, even though it is clear that this protein plays an important role in regulating virus replication and infection. This role is essential and therefore HIV-1 represents a novel target to initiate inhibitor design. Our objective is to elucidate the structure of HIV-1 Vif and its functional partners and thereby begin the investigation of the hypothesis that HIV-1 Vif might be a viable anti-viral target, either by inhibiting its function directly, its oligomerization state or through disrupting its cellular partners such as APOBEC3G. To perform this study we have assembled an interdisciplinary team of structural biologists and molecular virologists. We propose to use a combination of cross-linking, proteolysis, and mass spectrometry to determine particular specific interactions of Vif, APOBEC3G and their complex in solution at equilibrium. We propose three specific aims to begin this research track: (1) Elucidate the binding interfaces in HIV-1 Vif oligomerization; (2) Elucidate the binding interfaces in APOBEC3G oligomerization; (3) Elucidate the binding interfaces between HIV-1 Vif and APOBEC3G. [unreadable] [unreadable] [unreadable]