FIG 9.
Mapping of compound sensitivity in JUNV GP. (A) Schematic representation of GP chimeras between JUNV (strain XJ) and Cd1. (B) 293A cells incubated with JUNV XJ, Cd1, or chimera (C1X2 and X1C2) GP-pseudotyped lentiviral vectors, with DMSO or the indicated compounds being present. Relative titers are shown as percentages of the control titer (DMSO treated). Mean titers (in TU per milliliter) in DMSO-treated cells were as follows: 1.9 × 105 for JUNV XJ, 5.3 × 103 for Cd1, 2.4 × 104 C1X2, and 1.9 × 104 for X1C2. (C) Schematic representation of JUNV GP and the relative positions of the point mutations tested. The point mutations K33H and L420T (underlined) conferred the greatest degree of resistance to all three compounds. The drawing is not to scale and illustrates the interactions described previously by York et al. (61, 62). (D) 293A cells were incubated with JUNV GP-pseudotyped lentiviral vectors, either the wild type (WT) or the indicated mutants, in the presence of DMSO or the indicated compounds. Relative titers are shown as percentages of the control titer (DMSO treated). Mean titers (in TU per milliliter) on DMSO-treated cells were as follows: 1.9 × 105 for the wild type, 1.0 × 104 for the K33H mutant, 3.0 × 105 for the N37A mutant, 3.1 × 105 for the L420T mutant, 8.6 × 104 for the F427I mutant, 6.6 × 104 for the A435I mutant, and 2.9 × 105 for the F438I mutant. All data are the means ± standard deviations of results from 2 to 5 independent experiments. All data from panel B was statistically significant compared to the DMSO control (P < 0.001), and in panel D, statistical significance compared to the DMSO control is indicated (***, P < 0.001; ****, P < 0.0001).