Env mutations exhibit reduced syncytium formation and foster more efficient virus transmission.

(A) Schematic of virus transmission and cell-cell fusion events that result in luciferase expression upon co-culture of HIV-infected CEM-SS producer cells and CEM-luc target cells. In each scenario, HIV-1 Tat drives expression of an LTR-luciferase reporter gene in the CEM-luc target cells. Virus transmission is sensitive to RT inhibition by EFV because infection and de novo expression of Tat is required, whereas cell-cell fusion is resistant to EFV because preexisting Tat from an infected CEM-SS cell is able to activate reporter gene expression. (B) Total luminescence normalized to Gag expression and reported relative to the Vif-proficient virus. Each histogram bar represents the mean +/- SEM of the normalized data from 4 biologically independent experiments (p-values above each panel from one-way ANOVA and Fisher’s LSD test). (C) Luminescence signal attributable to cell-cell fusion or virus transmission for the indicated viruses. Cell-cell fusion events are quantified as the fraction of total luciferase signal that is resistant to EFV-treatment, and virus transmission events are quantified by subtracting the cell-cell fusion signal from the total luminescence signal. Each histogram bar represents the mean +/- SEM of 4 biologically independent experiments (p-values above each panel from one-way ANOVA and Fisher’s LSD test).