HIV Cell-to-Cell Spread Results in Earlier Onset of Viral Gene Expression by Multiple Infections per Cell

Cell-to-cell spread of hiv,a directed mode of viral transmission,has been observed to be more rapid than cell-free infection. however,a mechanism for earlier onset of viral gene expression in cell-to-cell spread was previously uncharacterized. here we used time-lapse microscopy combined with automated image analysis to quantify the timing of the onset of hiv gene expression in a fluorescent reporter cell line,as well as single cell staining for infection over time in primary cells. we compared cell-to-cell spread of hiv to cell-free infection,and limited both types of transmission to a two-hour window to minimize differences due to virus transit time to the cell. the mean time to detectable onset of viral gene expression in cell-to-cell spread was accelerated by 19% in the reporter cell line and by 35% in peripheral blood mononuclear cells relative to cell-free hiv infection. neither factors secreted by infected cells,nor contact with infected cells in the absence of transmission,detectably changed onset. we recapitulated the earlier onset by infecting with multiple cell-free viruses per cell. surprisingly,the acceleration in onset of viral gene expression was not explained by cooperativity between infecting virions. instead,more rapid onset was consistent with a model where the fastest expressing virus out of the infecting virus pool sets the time for infection independently of the other co-infecting viruses. © 2016 boullé et al.