in Chronically Infected Cells Is Associated Primarily with a Shift in RNA Splicing Patterns

We have analyzed the kinetics of human immunodeficiency virus type 1 (HIV-1) RNA induction in chronically infected T cells and promonocytes. A substantial amount of spliced mRNAs and assembled virions was found in resting cells. Induction increased the steady-state level of total HIV-1 RNA by 4-fold but increased the level of unspliced transcripts by 25-fold. This increase in unspliced RNA was reflected in the amount of virus seen by electron microscopy. These data suggest a mechanism for the induction of HIV-1 RNA in chronically infected cells involving a shift in splicing greatly favoring the stability of unspliced viral RNA with only a modest increase in total viral RNA. Analysis of the relative abundance of transcript classes is critical to the measurement of HIV-1 viral replication kinetics. We are interested in investigating the molecular mecha-nisms that mediate viral gene expression in human immuno-deficiency virus type 1 (HIV-1)-infected cells. Experiments in cells acutely infected with HIV-1 show an initial rise in the multiply spliced transcripts, tat, rev, and nef, followed by a rise in the level of both singly spliced and unspliced specie