GSE192724
Up-regulation of ATF4-LAMP3 axis by ORF45 facilitate lytic replication of Kaposi's sarcoma-associated herpesvirus
To investigate the regulation of ER stress-related gene expression by KSHV-ORF45 during lytic replication, we performed RNA-sequencing analysis of iSLK-BAC16 vs. iSLK-STOP45 cells under lytic induction for 72h. When the differentially expressed genes were filtered and analyzed, we found that ER stress-related gene expression was much low in iSLK-STOP45 cells compared with iSLK-BAC16 cells, indicating that ORF45 expression is required for induction of ER stress.To further reveal the signal transduction of LAMP3 in KSHV lytic replication, RNA-sequencing analysis was performed to identify the differentially expressed genes (DEGs) in normal vs. LAMP3-silenced cells under lytic replication. A total of 35372 raw read targets were obtained and all DEG clusters were filtered and analyzed by KEGG pathway enrichment analysis. Eleven pathway were significantly enriched over 10 fold in LAMP3-depleted cells compared with control cells, including PI3K-Akt signaling pathway.Given that Akt and ERK activation play the important roles in KSHV lytic replication, we conclude that LAMP3 might promote Akt and ERK activation and then consequently facilitate KSHV lytic replication. Overall design: mRNA profiles of iSLK-BAC16 vs. iSLK-STOP45 cells under lytic induction for 72h