Inhibition of X4-tropic HIV type 1 replication by knockdown of the cellular protein LEREPO4.

Human immunodeficiency virus 1 (HIV-1) and host cell factors show important mutual interactions. We found that HIV-1 infection induced expression of a likely ortholog of mouse immediate early response erythropoietin 4 (LEREPO4) in vitro. When LEREPO4 expression was suppressed by siRNA in P4-CCR5 cells, HIV-1 replication showed significantly reduced HIV-1 transcript and p24 protein levels as measured by quantitative PCR and ELISA, respectively. The LEREPO4 knockdown also had an inhibitory effect on HIV-1-LTR-driven reporter plasmid expression of β-galactosidase. Furthermore, the inhibitory effect of LEREPO4 silencing on HIV-1 replication was confirmed in Jurkat T cells. The up-regulation of LEREPO4 by HIV-1 and the inhibition of HIV-1 replication mediated by knockdown of LEREPO4 may point to an important functional role of LEREPO4 as a novel HIV-1 dependency factor.