Inhibition of HIV-1 replication by small interfering RNAs directed against glioma pathogenesis related protein (GliPR) expression.
BACKGROUND
Previously, we showed that glioma pathogenesis related protein (GliPR) is induced in CEM T cells upon HIV-1 infection in vitro. To examine whether GliPR plays a role as HIV dependency factor (HDF), we tested the effect of GliPR suppression by siRNA on HIV-1 replication.


RESULTS
Induction of GliPR expression by HIV-1 was confirmed in P4-CCR5 cells. When GliPR was suppressed by siRNA, HIV-1 replication was significantly reduced as measured by HIV-1 transcript levels, HIV-1 p24 protein levels, and HIV-1 LTR-driven reporter gene expression, suggesting that GliPR is a cellular co-factor of HIV-1. Microarray analysis of uninfected HeLa cells following knockdown of GliPR revealed, among a multitude of gene expression alterations, a down-regulation of syndecan-1, syndecan-2, protein kinase C alpha (PRKCA), the catalytic subunit beta of cAMP-dependent protein kinase (PRKACB), nuclear receptor co-activator 3 (NCOA3), and cell surface protein CD59 (protectin), all genes having relevance for HIV-1 pathology.


CONCLUSIONS
The up-regulation of GliPR by HIV-1 and the early significant inhibition of HIV-1 replication mediated by knockdown of GliPR reveal GliPR as an important HIV-1 dependency factor (HDF), which may be exploited for HIV-1 inhibition.
Capalbo
Gianni
G
Department of Hematology/Oncology and Infectious Diseases, J. W. Goethe-University Hospital, Theodor Stern Kai 7, Frankfurt/Main, Germany.
Müller-Kuller
Thea
T
Dietrich
Ursula
U
Hoelzer
Dieter
D
Ottmann
Oliver G
OG
Scheuring
Urban J
UJ
D000998:Antiviral Agents / Q000494:pharmacology*; D001688:Biological Products / Q000494:pharmacology*; D002460:Cell Line; D020869:Gene Expression Profiling; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D020411:Oligonucleotide Array Sequence Analysis; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology*; D014779:Virus Replication
D000998:Antiviral Agents; D001688:Biological Products; C094538:GLIPR1 protein, human; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering