Interaction between HIV-1 Vif and a Host Key Immune Regulator Component

Johns Hopkins University, Baltimore MD

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): In the absence of an effective HIV-1 vaccine, increasing the diversity of anti-retroviral medications to overcome the shortcomings of existing therapies is imperative. Understanding all interactions between cellular co-factors that bind HIV-1 proteins is important for the rational design of novel drugs that could inhibit critical interactions and reduce HIV-1 progression. We propose to characterize an interaction between Vif and a host immune regulatory component, core binding factor beta (CBF2). Our lab has recently established an association between these two proteins which is required for Vif to mediate degradation of host anti-retroviral factor, APOBEC3G. The proposed research seeks to test the hypothesis that there is a direct interaction between HIV-1 Vif and CBF2 which is mediated by unique regions on the surface of both proteins that are specific for their interaction. To test this assumption, I plan to construct Vif and CBF2 mutants using a multiple amino acid alanine substitution strategy to determine critical amino acids responsible for the interaction between the two proteins. In order to confirm and characterize a direct, physical interaction between Vif and CBF2, I will utilize isothermal titration calorimetry to determine the stoichiometry and strength of the interaction. PUBLIC HEALTH RELEVANCE: We propose to characterize an interaction between Vif and a host immune regulatory component, core binding factor beta (CBF2). Our lab has recently established an association between these two proteins which is required for Vif to mediate degradation of host anti- retroviral factor, APOBEC3G. Using an alanine scanning mutagenesis strategy and isothermal titration calorimetry, we will test our hypothesis that there is a direct interaction between HIV-1 Vif and CBF2 which is mediated by unique regions on the surface of both proteins that are specific for their interaction. Understanding the interactions between these two molecules will help improve the strategy for finding inhibitors that can block this interaction, thus providing a potential for novel anti-HIV drugs.