Cytomegalovirus miRNAs Target Secretory Pathway Genes to Facilitate Formation of the Virion Assembly Compartment and Reduce Cytokine Secretion

Lauren M. Hook, Finn Grey, Robert Grabski, Rebecca Tirabassi, Tracy Doyle, Meaghan Hancock, Igor Landais, Sophia Jeng, Shannon McWeeney, William Britt, and Jay A. Nelson

Cell Host & Microbe 15, 363–373, March 12, 2014

Speaker: Chia-Yi Hung (洪嘉依)                            Time: 14:00~15:00, Dec 10, 2014

Commentator: Dr. Shun-Hua Chen (陳舜華 老師)  Place: Room 601

Abstract:

One of the most significant and powerful advances in biomedical research has been the discovery of the ~22-nt-long class of noncoding RNAs designated microRNAs (miRNAs). These regulatory RNAs provide a special level of posttranscriptional gene regulation that controls a range of essential cellular processes. Several viruses, especially herpesviruses, encode miRNAs, and over 200 viral miRNAs have now been identified. For example, Human cytomegalovirus (HCMV) encodes multiple microRNAs (miRNAs) during lytic infection of cells, likely fine-tuning conditions important for viral replication. Current evidence further indicates that viruses use these miRNAs to manipulate both cellular and viral gene expression. As a result, the author wanted to study targets and functions about HCMV miRs UL112-1 together with US5-1, and US5-2. First, They used the RISC immunoprecipitation method followed by DNA microarray analysis (RIP-CHIP) to find that HCMV miRs UL112-1, US5-1, and US5-2 target multiple components of the host secretory pathway, including VAMP3, RAB5C, RAB11A, SNAP23, and CDC42. And then they transfected these miRNA (miRs UL112-1, US5-1, and US5-2) or siRNAs directed against RAB5C, RAB11A, SNAP23, and CDC42 into cell and gained the result that it caused the loss of Golgi stacks with reorganization into structures that resemble the VAC and a decrease in cytokine release. These observations indicate that multiple HCMV miRNAs coordinately modulate reorganization of the secretory pathway to facilitate formation of the VAC for efficient infectious virus production and control cytokine secretion.

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