HEV2 O‐16: Hepatitis E Seroprevalence in Europe: an assessment of serosurveys anti‐HEV IgG seroprevalence in Europe: a meta‐analysis

sequencing. RNA-Seq was performed on Ion-PGM using platform specific protocol. Sequences were aligned to genome build HG19 using TOPHAT2 and BOWTIE2 in Partek Flow. Mapped sequences were analysed in Partek Genomic Suite for differential expression. A total of 412 genes were differentially expressed compared to control by 1.5 times (p < 0.05). Gene ontology analysis has shown majority genes grouped under anti-apoptotic, cell survival, signal transduction, inflammatory and cytoskeletol reorganization pathways. The most highly differentiated genes were those regulating apoptosis and immune clearance. Upregulated antiapoptotic genes include BIRC7, BCLb, CASP12 and TBX2, while highly down regulated pro-apoptotic genes include TIMD4, IL20RA, NTRK1, DOK2 and CEACAM3. Several anti-viral and pro-inflammatory genes were highly differentially expressed, BPIFB1, GPR15, ADRB2, SELL, OASL and IRF8. TGFb signaling pathway was highly enriched in our analysis, differential expression of SOSTDC1, DAND5, KCP, AMN, TBX2, ID1 and CSNK1G2-AS1 overall leading to inhibition of TGFb/BMP pathway. The data indicated an active reorganization of cytoskeletol elements. There was a clear indication of downregulation of actin polymerization and membrane integrity, and up regulation of microtubule formation and dynamics. TMSB15B, which is known to inhibit actin polymerization was highly upregulated. Genes involved in actin regulation like FGD5, MYO1H and SEMA3E were downrgulated. Genes shown to bind to cytoskeletol elements like GRID2IP, GAS2L2, CORO6, KIF9, CORO1B were upregulated. HEV genome is known to elicit a strong innate immune response, which in our present analysis is found to be circumvented by pORF3 by strongly supporting anti-apoptotic signalling. Essentially, ORF3 buys time for HEV genome to replicate, package and exit the cell. In addition ORF3 helps reorganize cytoskeletol elements for a polarized exit of HEV preferentially to the bile canaliculi.