Novel microRNAs and alternative isoforms arising during human cytomegalovirus infection

Abstract

Human cytomegalovirus (HCMV) is the main viral cause of birth defects, often leading to neurological disorders, but the underlying molecular mechanisms are poorly characterized. To advance our understanding of the complex virus‐host transcriptional landscape present during infection, we have completed a suite of comprehensive transcriptome‐focused studies using HCMV‐infected human fibroblasts and neural stem cells. Through deep sequencing analysis of small RNAs, we have refined viral miRNA annotations, identified novel HCMV miRNAs, and observed significantly upregulated host miRNAs. We also sequenced Argonaute‐associated RNAs (Ago CLIP‐seq) to obtain direct evidence for incorporation of all HCMV miRNAs into the endogenous host silencing machinery. High‐throughput sequencing of polyadenylated mRNAs (RNA‐seq) has enabled us to identify novel spliced HCMV transcripts and hundreds of human genes that are alternatively spliced upon infection. Our findings will enable the elucidation of improved therapeutic targets in the near future.This work was supported by grants from the U.S. National Institutes of Health (HG004659 and GM084317), the California Institute for Regenerative Medicine (RB3‐05219), and the Stem Cell Program at UCSD.