HIV-1 Capsid-Cyclophilin Interactions Determine Nuclear Import Pathway, Integration Targeting and Replication Efficiency (original) (raw)
Figure 4
Residue changes in HIV-1 CA mutants alter integration site targeting.
A, Effects of CA mutants on integration frequency near multiple chromosomal features. The rows show genomic features, and the columns indicate integration site data sets. The color code indicates ROC areas [34]. The arrow denotes the wild type control set used for pairwise statistical comparisons to the other data sets. P values summarizing the significance of departures from the control are represented by asterisks (*P<0.05; **P<0.01; ***P<0.001). Several different intervals are compared. "Expression density" summarizes the density of genes in the indicated length intervals that are expressed in the upper half ("top 1/2") or upper sixteenth ("top 1/6") of all genes on Affymetrix HU95A chip data for HeLa cells (accessions GSM23372, GSM23373, GSM23377, and GSM23378). For a more detailed guide see [16]. B, ROC area values were used to generate pairwise Euclidean distances, which were then analyzed by hierarchical clustering generating the presented dendogram. The locations of changed residues in mutant viruses studied on C, the CA hexamer (PDB:3GV2) and D, the CA monomer (PDB:3GV2). E, Time course of replication competent NL4.3 (Ba-L Env) bearing wild type, P90A or N74D CA in HeLa TZM-bl cells. Luciferase expression was measured by counting RLU at indicated times after virus inoculation. The data are representative of two independent experiments. F, Replication assay of NL4.3 (Ba-L Env) bearing wild type or CA mutants P90A or N74D in human MDM. Cells were stained for Gag p24 at specific time points after infection and infected colonies counted. Standard errors of the mean of three fields are shown.