Effect of mdv1-miR-M4 and Related MicroRNAs On Expression of Innate Immune Response Genes In Chicken Embryo Fibroblasts
Date
2017-05
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
Abstract
MicroRNAs (miRNAs) have been shown to post-transcriptionally regulate
gene expression. Past studies have shown that Marek’s disease virus (MDV) has
multiple miRNAs in its genome. MDV1-miR-M4 is a particularly important miRNA
found in MDV serotype 1 and this miRNA has been implicated in T cell lymphoma
formation caused by MDV. MDV1-miR-M4 shares a seed sequence with miR-155,
which is another oncogenic miRNA. MiR-155 is found across phylogeny. We inserted
mdv1-miR-M4, the meq miRNA cluster, as well as miR-155 into the genome of
herpesvirus of turkeys (HVT) in order to study the functions of these miRNAs since
the non-recombinant parent HVT does not express them. The expression levels of
interferons (IFNs), including IFN-alpha, IFN-beta, and IFN-lambda were examined
post-infection. IFN-alpha and IFN-beta were not induced under the experimental
conditions, and IFN-lambda was induced at approximately 48 hours post-infection.
We also examined expression of IFN-inducible genes. Expression of the IFNinducible
genes MX-1 and OAS-3 was elevated in some instances under the
experimental conditions. Expression of MX-1 and OAS-3 is typically type I IFN
dependent, but in this case elevation was observed in the absence of induction of IFNalpha and/or IFN-beta. Inhibition of MX-1 and OAS-3 induction by meq miRNAs and
miR-155 when compared to infection with parent HVT was seen at 30 minutes, and at
3, 6, 15, 24, and 48 hours post-infection The results suggest that meq miRNAs,
including MDV1-miR-M4 and the MDV1-miR-M4 analog, oncogenic miR-155,
contribute to inhibition of innate immune responses.
Description
Keywords
Biological Sciences, Molecular Biology, Cell biology, mdv1-miR-M4 ,MicroRNAs, Expression of Innate Immune Response Genes, Chicken Embryo Fibroblasts