engleski

A subset of host miRNAs is upregulated during herpes simplex virus 1 infection

Many viruses alter the expression of specific host microRNAs (miRNAs) to facilitate their replication or establish and maintain latency. Herpes simplex virus 1 (HSV-1) encodes a large number of miRNAs and it has been shown to impact host miRNA expression during productive infection. We sequenced small-RNAs from the productively infected HFFs at different times after infection and observed changes in expression levels for many miRNAs, however levels of only a few were changed for more than 3x ; and among these were three miRNAs expressed from a single cluster, miR-183/96/182. In addition, we analysed the expression levels of eight cellular miRNAs, previously reported deregulated in HSV-1 infection or found in our screen, in three cell lines (human embryonic kidney cells HEK293, neuroblastoma cells SH-SY5Y, human fibroblasts WI38) and two primary cells (human foreskin fibroblasts HFFs and mouse bone marrow derived macrophages BMDM) at different time points after infection. Surprisingly, we only detected a significant change of miR-182, miR-96 and miR-183 in fibroblasts (WI38 and HFFs ; ~10x). Our preliminary results show that the upregulated cellular miRNAs, as well as HSV-1 expressed miRNAs, are loaded successfully onto RISC complex, which might indicate their function. Indeed, we observed decreased protein levels for several predicted targets of miR-182, miR-96 and miR-183, among which is forkhead box O1 (FOXO1), which coincides with the increased expression of these miRNA However, using CripR/Cas9 technology we were able to show that members of the FoxO protein family are required for the efficient virus replication.

HSV-1, host microRNA, microRNA targets

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