COMPARATIVE TRANSCRIPTOMIC PROFILING OF EPITHELIAL CELLS INFECTED WITH WILD AND ATTENUATED VARIANTS OF RUBELLA VIRUS

Rubella virus (RV) causes mild illness. However, RV infection during the critical stages of fetal organ development lead to congenital rubella syndrome. The host factors associated with the RV teratogenicity are unknown. In this work, the effect of infection with wild (w) and attenuated (att) variants of the laboratory strain C-77 of RV on gene expression in A549 lung epithelial cells was compared via RNA sequencing. Libraries for sequencing were prepared using the TruSeqRNA Library Preparation Kit v2 (Illumina, USA). Sequencing was performed on the NextSeq500 (Illumina) platform.

In cells infected with C-77att, 1,088 genes were down-regulated and 1,096 were up-regulated, compared with 825 down-regulated and 928 up-regulated genes in cells infected with C-77w. The most up-regulated genes in С-77att-infected cells were IFNL1-4, IFNB1, TLR3, CXCL10, CXCL11, IFIT2, RSAD2, IDO1, OASL, OAS2, TNFSF13B, CASP1, CCL4, CCL5, ISG15, ISG20, IFI27, TRIM22, XAF1, TNFSF10, NCF2, LGALS9, USP18, CD274, EGR1, BST2, KRT17, GBP1-5, UBA7, CX3CL1, HSPA1A, and HSPA1B. These genes are mainly responsible for the production of interferons and chemokines, post-interferon response, apoptosis signaling, and unfolded protein response. In contrast, the most differentially up-regulated genes in C-77w-infected cells were genes, namely, TXNIP, CA9, PTPRN2, TGFBI, PTPRN2, SMOC1, BMP6, NDR1, PTPRN2, CCN5, MAPT, NTRK3, NDRG1, ADGRG1, SDK2, SMOC1, and DKK1, involved in the processes of morphogenesis and embryogenesis, including neuronal, glial, heart, and visual system development, whereas infection with the attenuated variant did not affect the expression of these genes.

Thus, a comparative analysis of gene expression in RV-infected A549 cells revealed that the attenuated variant predominantly caused activation of genes responsible for the immune response, while the wild variant additionally activated the expression of genes involved in gliogenesis and morphogenesis, indicating molecular mechanisms that could potentially be involved in the teratogenic effect of RV.