Human herpesvirus 8 cellular gene modulation

P0663 Human herpesvirus 8 cellular gene modulation Barbara Matteoli* 1 , Rita Romano 2 ,FrancescaTabacchi 2 , Moreno Ferroni 1 1 LAMM,SRL,Lucca, Italy, 2 Department of Public Health and Infectious Diseases,Sapienza University of Rome, Rome, Italy Background:Sinceinflammation is the basis of viral pathogenesis and may beinduced either directly by thevirus or by thecell in responseto infection, theexpression pattern of cellular genes involved in this process was investigated in human epithelial and lymphoid cells infected with Human herpes virus 8 (HHV8) . Materials/methods:Theexpression of 297 human genes involved in 65 pathways associated with inflammation have been studied in HEK293 and PBMC cells 24h after infection with HHV8 (A1 and C3 strains) by DualChip Microarray.Signal quantification was performed by SilverQuant Image Viewer and analysis software(Eppendorf, Germany) and SPSS 16.0 for Windows (SPSS, USA) with two way ANOVA followed by Scheffecontrast. Results:Expression ratios of most of the genes werecloseto 1 or changed only <2-fold cutoff (in positive or negativevalue), suggesting that they were not significantly changed in consequenceto HHV8 infection. Overall,a higher number of genes resulted modulated in HHV8-infected HEK293 cells with respect to PBMCs. A robust increasein theexpression was found in genes involved in inflammation (i.e., AGT, CCR8, CXCR4, IL-6, IL-9, IL10RA, IL-17, IL-23A), signal transduction (i.e.,FGF5,FGF7, MAP3K1, MAPk9m TGFBR1,TRAF2),cellular cycle(IGFBP1), immuneresponse(i.e., IL-16,TLR4),apoptosis (TNFSF4,TNFSF11),and others genes belonging to different categories (i.e., BMP4, BMPR2,EPHA3, HGFBP1, RUNX1, RUNX2,SP1).With a >2-fold threshold filter gene modulation as significant,a high numbers of genes resulted significantly modulated both in HEK293 cell lineand PBMCs infected both with the A1 (169 and 104 genes, respectively) and C3 subtypes (131 and 93 genes, respectively). Next, to increasethesignificance, only those genes with >4-fold changes in their expression were considered. A total of 24 genes resulted strongly induced,especially after A1 subtypeinfection.Thecomparison of transcriptional profiling between both viral subtypes showed that only 4 genes arestrongly induced by different viral subtypes (i.e., BMP4, BMPR2, RUNX2 and TNFSF11). Conclusions: New human genes have been involved in HHV8 infection;commonly modulated genes may be used as target for antiviral/chemiotherapic treatmen