Human immunodeficiency virus type 2 capsid protein mutagenesis defines the determinants for Gag-Gag interactions

Human immunodeficiency virus (HIV) Gag drives particle assembly. The capsid (CA) domain is critical for Gag oligomerization, and encodes key residues that dictate Gag-Gag interactions and particle morphology. The immature particle morphology of HIV-2 is intriguing different relative to that of HIV-1. To help define the critical determinants for Gag-Gag interactions and investigate the differences between HIV-1 and HIV-2, we have conducted mutagenesis in targeted locations of HIV-2 CA that have been implicated in Gag-Gag interactions. In particular, a panel of 31 site-directed mutants at the HIV-2 CA inter-hexamer interface, intra-hexamer interface and CA inter-domain linker have been created and analyzed for the efficiency of particle production, particle morphology, particle infectivity, Gag subcellular distribution and in vitro protein assembly. Seven conserved residues (L19A, A41, I152, K153, K157, N194, D196) and two non-conserved residues (G38, N127) were found that impact Gag multimerization and particle assembly. Taken together, these observations complement structural analyses of immature HIV-2 particle morphology and Gag lattice organization, and provide insights into the morphological differences between HIV-1 and HIV-2 immature particles and their impact on virus replication. ### Competing Interest Statement The authors have declared no competing interest.