HIV-1 Gag major homology region (MHR)

The HIV-1 Gag major homology region (MHR) is a highly conserved 20-amino acid sequence located within the C-terminal domain (CTD) of the capsid (CA) protein (UniProt: P04591). This motif is nearly universal among orthoretroviruses, suggesting a fundamental role in the viral life cycle and structural integrity (PubMed: 8120549). Biologically, the MHR is essential for the proper assembly of the immature Gag polyprotein lattice and the subsequent formation of the mature, infectious viral core during the budding process (PubMed: 15564416). Mutations within the MHR typically result in severe assembly defects, leading to the production of non-infectious, morphologically aberrant virions or a complete failure in particle release (PubMed: 9223631). Due to its high degree of conservation and critical structural function, the MHR is a significant target for the development of capsid assembly inhibitors (PubMed: 27129250). Therapeutic interventions targeting this region, such as experimental peptides and small molecules, aim to disrupt the protein-protein interactions necessary for viral replication. While clinical capsid inhibitors like Lenacapavir target broader interfaces, the MHR remains a focal point for research into next-generation antiretroviral therapies.

Other names

Gag MHRCapsid major homology regionCA MHRMajor homology region of HIV-1 Gag

Inhibition of Gag multimerization and viral capsid assembly by disrupting protein-protein interactions within the major homology region, preventing the formation of infectious virions.