Fig. 7: PBS and polyA regulate HIV-1 dimerization, Pr55Gag binding and genome packaging.
From: Short- and long-range interactions in the HIV-1 5′ UTR regulate genome dimerization and packaging
a, PBS targeting oligos can trigger dimerization of a 3G RNA. cPBS(182–199) disrupts the TAR–PBS interaction leading to the formation of a higher order RNA structure. cPBS(199–216) disrupts the PAS-anti-PAS stem and enhances dimerization. The effects of both oligos are additive. Experiments were performed in duplicate, with representative data shown. b, Mutations targeting the polyA–SL1 and PBS–SL1 interaction affect Pr55Gag binding as measured by MST. Data from three independently experiments were analyzed. Data are represented as mean with error bars showing standard deviations. c, Competition assays to measure the relative effects of mutations on genome packaging into virions. Two-way competition assays show that dimer promoting mutations C218G and C84A–C85A are enhanced in genome packaging compared to monomer promoting mutations A220G–G221A and U86G–A89C. Five-way competition assays between WT HIV-1 and mutants show that dimer promoting mutants are packaged similar or better than WT, whereas monomer promoting mutants are packaged less efficiently than WT. Experiments were performed in duplicate. d, Model showing how the binding of host factors can regulate viral replication, in part, through remodeling RNA structure.
