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  • Title: Maturation inhibitors facilitate virus assembly and release of HIV-1 capsid P224 mutant.
    Author: Timilsina U, Ghimire D, Adhikari LP, Bhattarai A, Mishra N, Rai M, Dubey RC, Gaur R.
    Journal: Virology; 2018 Aug; 521():44-50. PubMed ID: 29879541.
    Abstract:
    HIV-1 Maturation inhibitors (MIs) bind to the C-terminal domain of capsid protein (CA-CTD) and spacer peptide 1 (SP1) in HIV-1 Gag and inhibit the CA-SP1 cleavage by stabilizing the immature Gag. The β-turn motif, GVGGP in the HIV CA-CTD (residues 220-224) is one of the key determinants of HIV Gag assembly. In the present study, we mutated each residue of HIV-1 β-turn motif to alanine and observed complete inhibition of virus release of all mutants. This defect in virus release was rescued in the presence of maturation inhibitors; BVM and PF-46396 for P224A mutant. To our knowledge, this is the first report of identification of BVM and PF-46396-dependent capsid mutant. Our results highlight the importance of the core β-turn motif residues in immature virus assembly and suggest that the presence of MIs enhances Gag membrane binding and multimerization thereby restoring virus release of HIV Gag P224 mutant.
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