HIV-1 Envelope glycoprotein cytoplasmic tail – Gag matrix domain interface (Env-CT – MA interface)

The HIV-1 Envelope glycoprotein cytoplasmic tail (Env-CT) – Gag matrix domain (MA) interface is a critical protein-protein interaction required for the assembly of infectious HIV-1 particles [1]. The Env-CT is the C-terminal portion of the gp41 transmembrane protein, which is unusually long in HIV-1 compared to other retroviruses and contains specific motifs essential for its recruitment to assembly sites [2]. During viral budding, the MA domain of the Gag polyprotein interacts with the Env-CT to ensure that Env trimers are incorporated into the nascent virion at the plasma membrane [1, 2]. Disruption of this interaction, either through mutations or inhibitory molecules, leads to the production of virions that lack Envelope spikes and are therefore non-infectious [3]. This interface is considered a promising therapeutic target because it is vital for the viral life cycle and involves highly conserved structural requirements within the matrix domain [2]. Although no drugs targeting this specific interface are currently FDA-approved, research into small molecules and peptide-based inhibitors is ongoing to block this step of the viral assembly process and prevent the spread of infection [3]. (Sources: [1] Tedbury, P. R., & Freed, E. O. (2015). "The Role of the HIV-1 Envelope Glycoprotein Cytoplasmic Tail in Virion Assembly." Journal of Molecular Biology; [2] Alfadhli, A., et al. (2019). "The HIV-1 Gag-Matrix Protein-Envelope Glycoprotein Cytoplasmic Tail Interaction." Journal of Virology; [3] Murphy, R. E., et al. (2021). "Small-molecule inhibitors of the HIV-1 Env-MA interaction.")

Other names

gp41 CT – MA interactionEnv-Gag interfaceHIV-1 Env-MA interactiongp41 cytoplasmic tail – p17 matrix interfaceEnvelope-Matrix protein-protein interaction

Inhibition of Envelope glycoprotein incorporation into budding virions by disrupting the physical interaction between the gp41 cytoplasmic tail and the Gag matrix domain.