Figure 3

Viral attachment receptors. (A) Heat maps showing differentially expressed genes encoding viral attachment receptors and their downstream signaling molecules. The intensity of the color indicates the degree of expression level. Range of the logFC is presented in the scale. Gene expression was considered as significant only when the LogFC was beyond ± 1.2, average logCPM (count per million) was > 3, and p-value was < 0.01. An edgeR package was used for statistical analysis of differentially expressed gene. The unshrunk.logFC and false discovery rate (FDR) values for each genes are presented in Supplementary Dataset. (B) Attachment of flaviviruses to entry receptors evoke various pathways like endocytosis, changes in cell cytoskeleton via integrins/Rac-1-myosin2, cell survival signaling via PI3K-AKT (TIM and TAM receptors), suppression of immune response via JAK-STAT and activation of SOCS-1/3 (mediated through TAM receptors), which help for viral infectivity. Expression of IFNAR1, IFNAR2 and integrin αv did not altered in our study (yellow squares present no significant deregulation). None of the member of TIM family was detected (black dash indicates no detection of gene in our study). Expression of MERTK and AXL (TAM) were upregulated significantly by rDIII-TBEV and rDIII-WNV, respectively (green arrows indicate significant upregulation). Activation of TAM typically induces PI3K-AKT pathway. Note that, expression molecules in JAK-STAT signaling pathway (e.g. JAK3 and STAT4) were upregulated instead of genes in PI3K-AKT signaling (expression of AKT2, PIP5K1C, PIK3CB and PPP2R1B unchanged by rDIII-TBEV and downregulated by rDIII-WNV). Red arrows indicate downregulation of genes involved in given pathway. Activation of JAK-STAT promotes expression of SOCS1 and 3 (beneficial for the virus entry and replication). Both SOCS1 and SOCS3 genes were also upregulated by rDIII of TBEV or WNV.