HIV-1 Viral Infectivity Factor–ElonginC protein–protein interaction interface (HIV-1 Vif–EloC PPI interface) (HIV-1 Vif–EloC PPI interface)

The HIV-1 Viral Infectivity Factor (Vif)–ElonginC protein–protein interaction interface is a critical structural site for the survival of the Human Immunodeficiency Virus type 1 (HIV-1) within host cells. Vif is an accessory protein that hijacks the host's Cullin-5 (Cul5) E3 ubiquitin ligase complex by directly binding to ElonginC and ElonginB via its BC-box motif [1.1.2, 1.4.1]. This recruitment allows Vif to target the host antiviral protein APOBEC3G (A3G) for polyubiquitination and subsequent proteasomal degradation, effectively neutralizing a key component of the innate immune response [1.4.3, 1.4.4]. Without Vif-mediated degradation, A3G would induce hypermutation in the viral genome during reverse transcription, leading to non-functional viral progeny [1.4.1, 1.4.5]. As a therapeutic target, the Vif–ElonginC interface offers a strategy to restore the host's natural defenses against HIV-1 [1.3.1]. Small molecule inhibitors like VEC-5 are designed to disrupt this specific protein-protein interaction, preventing the assembly of the Vif-Cul5 complex and thereby stabilizing A3G levels to inhibit viral replication [1.3.1, 1.5.2]. Challenges in targeting this interface include ensuring high specificity to avoid disrupting the physiological roles of ElonginC in other cellular complexes, such as the Von Hippel-Lindau (VHL) tumor suppressor complex [1.4.1].

Other names

Vif-EloC interfaceVif-Elongin C complexVif-BC complex interfaceVif-EloBC interactionVif-SOCS box-ElonginC interaction

Inhibition of protein-protein interaction (PPI inhibitor); specifically blocks the binding of the HIV-1 Vif BC-box motif to the host ElonginC protein, preventing the assembly of the Vif-Cullin5-ElonginB-ElonginC E3 ubiquitin ligase complex and thereby stabilizing host restriction factors like APOBEC3G.