Human immunodeficiency viruses type 1 and 2 (HIV-1 and 2) are known to depend on cellular host machinery for their replication and survival. While most of the studies on cellular proteomic and transcriptomic changes focused on the late-phase of the infection, studies of those changes in the early time-points; especially in the case of HIV-2 infection, are widely lacking. Using 2nd generation HIV-1 and 2 VSV-G pseudotyped lentiviral vectors, we transduced HEK-293T cells, and carried out transcriptomic profiling and proteomic analysis of harvested cells at 2h time point, which is representative of the immediate early-phase events in the infection cycle.