Involvement of human topoisomerase II isoforms in HIV-1 reverse transcription

Abstract

HIV-1 reverse transcription (RTn) involves synthesis of double strand DNA (dsDNA) from viral genomic RNA. Topoisomerase II (Topo II) alpha and beta maintains topological reorganization of dsDNA regions and catalytic inhibition of these isoforms repressed viral replicative cycle. Present study is aimed to understand the role of Topo II isoforms in HIV-1 early replication. Topo IIα and β showed differential expression in SupT1 cells and PBMCs during early hours of HIV-1 infection where Topo IIα expression increased after 4h, while Topo IIβ showed relatively higher expression at 1 and 4h. In Topo IIα and/or β down regulated cells, transcription of viral genes gag, pol and env as well as proviral DNA synthesis was abolished. In Topo IIα and/or β down regulated cells, strong stop DNA synthesis was unaffected while other downstream events of reverse transcription such as first strand transfer, full length minus strand synthesis, and second strand transfer were completely inhibited, which affects HIV-1 replication. Further, co-localization of Topo II isoforms with HIV-1 reverse transcriptase was observed in SupT1 cells and PBMCs by immunofluorescence. These results collectively suggest a role of Topo II isoforms during HIV-1 RTn probably by promoting the alignment of viral RNA-DNA hybrids.