Objective: To unravel the interplay between HIV-1 and its host cell, the effect of HIV-1 infection on cellular gene expression was investigated. Methods: HIV-1(SF33)-infected and uninfected H9 T cells were screened by differential display and RNase protection assay. The finding (PDS5A) was confirmed in HIV-1(Lai)-infected P4-CCR5 HeLa cells, which were also examined after PDS5A siRNA knockdown in regard to HIV-1 replication by quantitative RT-PCR, p24 ELISA and LTR-driven beta-galactosidase expression. The PDS5A knockdown effect on cellular gene expressions was studied by microarray analysis. PDS5A tissue expression was determined by Northern blotting. Results: Regulator of cohesion maintenance, homolog A (PDS5A) was found to be down-regulated by HIV-1. When PDS5A was suppressed by siRNA, HIV-1 replication was unaffected. PDS5A was found to be highly expressed in skeletal muscle tissue, and to lesser degrees in pancreas, heart, placenta, lung, kidney, liver and brain. Microarray analysis of PDS5A knockdown revealed 91 differential gene products over-representing cell cycle, transport and protein stability regulation, including 4 genes (PP2A, RANTES, PCAF, TCF7L2) previously reported to interact with HIV-1. Conclusion: The data show a downregulation of proliferation-associated host gene PDS5A and suggest a role of PDS5A in HIV-1-induced cellular pathogenesis but not viral replication. Copyright (C) 2011 S. Karger AG, Basel