Comparative analysis of differential cellular genome and proteome regulation by HIV-1 and HIV-2 pseudovirions in the early phase of infection
In spite of the similar structure and genomic organization of human immunodeficiency viruses type 1 and 2 (HIV-1 and HIV-2), striking differences exist between them in terms of replication dynamics and clinical manifestation of infection. Although the pathomechanism of HIV-1 infection is well characterized, relatively few data are available regarding HIV-2 viral replication, and its interaction with host-cell proteins during the early phase of infection. We utilized proteo-transcriptomic analyses to determine differential genome expression and proteomic changes induced by transduction with HIV-1 / 2 pseudovirions during 8, 12, and 26 hour time-points in HEK-293T cells. We show that alteration in the cellular milieu was indeed different between the two pseudovirions. The significantly higher number of genes altered by HIV-2 in the first two time-points, suggest a more diverse, yet subtle effect on the host cell, preparing the infected cell for integration and latency. On the other hand, GO analysis showed that, while HIV-1 induced cellular oxidative stress and had a greater effect on the cellular metabolism, HIV-2 mostly affected genes involved in cell adhesion, extracellular matrix organization or cellular differentiation. Proteomics analysis revealed that HIV-2 significantly downregulated the expression of certain proteins that perhaps benefited its life-cycle and latency. Meanwhile HIV-1 influenced the cellular level of oxidative stress and cell death involved proteins.  Our study provides an insight into the understudied replication cycle of HIV-2 and enrich our knowledge about the use of HIV-based lentiviral vectors in general. Overall design: To investigate the gene regulatation in the early phase of infection,we  performed RNA sequencing on HEK293T cells transduced with HIV-1, HIV-2, and mock pseudovirions at three time points following transduction (8, 12, 26 hours).