Different microRNA Alterations Contribute to Diverse Outcomes Following EV71 and CA16 Infections: Insights from High-Throughput Sequencing in Peripheral Blood Mononuclear Cells of Rhesus Monkey. Macaca mulatta

Enterovirus 71 (EV71) and Coxsackievirus A16 (CA16) are the predominant etiological agents of hand, foot, and mouth disease (HFMD) and both belong to the human enterovirus A species of the Picornaviridae family. These viruses share similar genetic homology, although the clinical manifestations of HFMD caused by the two viruses have some discrepancies. Furthermore, the underlying mechanisms leading to these differences remain unclear. microRNAs (miRNAs) participate in numerous biological or pathological processes, including host responses to viral infections, by targeting messenger RNAs (mRNAs) for translational repression or degradation. Here, we focused on differences in miRNA expression patterns in peripheral blood mononuclear cells (PBMCs) of rhesus monkeys infected with EV71 or CA16 at different time points using high-throughput sequencing technology. For the first time, this study demonstrated that EV71 and CA16 infection result in specific miRNA expression patterns in PBMCs. Overall design: The EV71 virus strain (sub-genotype C4, GenBank: EU812515.1) that originated from an epidemic in Fuyang, China in 2008 and the CA16 virus G20 strain (sub-genotype B, GenBank: JN590244.1), which originated from an HFMD patient in Guangxi in 2010, were propagated in PBMCs at a multiplicity of infection (MOI) of 1 the following day. Cells were infected in triplicate and collected at 0, 24 and 48 hours post infection (hpi). Cells infected with EV71 and CA16 for 0 hpi were used as controls. We defined the different experimental groups as EV71-0h, EV71-24h, EV71-48h, CA16-0h, CA16-24h and CA16-48h.