Rhesus cytomegalovirus encodes seventeen microRNAs that are differentially expressed in vitro and in vivo

Abstract

Human cytomegalovirus (HCMV) miRNAs are important for regulation of viral infection and evasion of host immune responses. Unfortunately, the importance of HCMV miRNAs cannot be addressed in vivo due to the species specificity of CMVs. Rhesus CMV (RhCMV) infection of rhesus macaques provides an important model system for HCMV pathogenesis due to the genetic similarity between the viruses. In this report, seventeen RhCMV miRNAs were identified using Next Generation Sequencing. In fibroblasts, RhCMV miRNAs associate with Argonaute proteins and display several patterns of expression, including an early peak in expression followed by decline and accumulation throughout infection. Additionally, RhCMV encodes an HCMV miR-US5-2 homologue that targets the 3' UTR of RhCMV US7. Finally, examination of salivary gland tissue from infected animals revealed the presence of a subset of viral miRNAs. This study highlights the importance of the RhCMV model system for evaluating the roles of CMV miRNAs during viral infection.