PLX075966

GSE79029: KSHV Infection Mimics the Hypoxic Response Based on Next-Generation Sequencing [mRNA-Seq]

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

Purpose: Kaposis sarcoma associated-herpesvirus (KSHV) causes several hyperproliferative disorders, including Kaposis sarcoma, primary effusion lymphoma and multicentric Castlemans disease. KSHV encodes for a number of microRNAs (miRNAs), and KSHV infection can affect the expression of cellular miRNAs. Hypoxia has been shown to induce KSHV reactivation, directly induce several KSHV lytic genes, and also induce the most abundant latent viral protein, LANA. Also, several KSHV proteins can stabilize and increase the cellular levels of hypoxia-inducible factor (HIF-1). However, the degree to which hypoxic pathways are utilized by KSHV has yet to be determined.; Methods: We investigated the interplay between hypoxia and KSHV infection by comparing the 31effects of hypoxia and KSHV infection on miRNA and mRNA expression, and by examining the 32effects of hypoxia on uninfected and KSHV-infected cells. This was accomplished using next-33generation sequencing (NGS), qRT-PCR, Taqman assays, and pathway analysis.; Results: NGS analysis of human mRNAs revealed striking similarities (~34%) between the transcriptomic response to hypoxia and the transcriptomic response to KSHV infection. Additionally, hsa-miR-210, a key hypoxia-inducible miRNA with pro-angiogenic and anti-apoptotic properties, was found significantly up-regulated by both KSHV infection and hypoxia using Taqman assays. Finally, KSHV infected cells differed somewhat in their response to hypoxia compared to KSHV-uninfected controls.; Conclusions: These results demonstrate that KSHV harnesses a part of the hypoxic cellular response and induces miR-210 up-regulation. The understanding of how these miRNAs, genes and pathways are regulated by HIF-1 and KSHV infection are essential to a better understanding of the biology of KSHV-associated diseases. SOURCE: Coralie Viollet NIH/NCI