ABSTRACT
BACKGROUND: Non-human primates (NHPs) are important models of medical research on obesity and cardiovascular diseases. As two of the most commonly used NHPs, cynomolgus macaque (CM) and African green monkey (AGM) own different capacities in lipid metabolism of which the mechanism is unknown. This study investigated the expression profiles of lipid metabolism-related microRNAs (miRNAs) in CM and AGM and their possible roles in controlling lipid metabolism-related gene expression. METHODS: By small RNA deep sequencing, the plasma miRNA expression patterns of CM and AGM were compared. The lipid metabolism-related miRNAs were validated through quantitative reverse-transcription (RT) polymerase chain reaction (PCR). Related-target genes were predicted by TargetScan and validated in Vero cells. RESULTS: Compared to CM, 85 miRNAs were upregulated with over 1.5-fold change in AGM of which 12 miRNAs were related to lipid metabolism. miR-122, miR-9, miR-185, miR-182 exhibited the greatest fold changes(fold changes are 51.2, 3.8, 3.7, 3.3 respectively; all P < 0.01). And 77 miRNAs were downregulated with over 1.5-fold change in AGM of which 3, miR-370, miR-26, miR-128 (fold changes are 9.3, 1.8, 1.7 respectively; all P < 0.05) were related to lipid metabolism. The lipid metabolism-related gene targets were predicted by TargetScan and confirmed in the Vero cells. CONCLUSION: We report for the first time a circulating lipid metabolism-related miRNA profile for CM and AGM, which may add to knowledge of differences between these two non-human primate species and miRNAs' roles in lipid metabolism.
Subject(s)
Chlorocebus aethiops/genetics , Lipid Metabolism/genetics , Lipids/blood , Macaca fascicularis/genetics , MicroRNAs/genetics , ATP Binding Cassette Transporter 1/blood , ATP Binding Cassette Transporter 1/genetics , Animals , Carnitine O-Palmitoyltransferase/blood , Carnitine O-Palmitoyltransferase/genetics , Chlorocebus aethiops/blood , F-Box-WD Repeat-Containing Protein 7/blood , F-Box-WD Repeat-Containing Protein 7/genetics , Fatty Acid Synthase, Type I/blood , Fatty Acid Synthase, Type I/genetics , Gene Expression Profiling , Gene Expression Regulation , Gene Ontology , High-Throughput Nucleotide Sequencing , Macaca fascicularis/blood , MicroRNAs/blood , Molecular Sequence Annotation , Protein Isoforms/blood , Protein Isoforms/genetics , Receptors, Lipoprotein/blood , Receptors, Lipoprotein/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sterol O-Acyltransferase/blood , Sterol O-Acyltransferase/genetics , Vero CellsABSTRACT
Animal models are critical to understand disease and to develop countermeasures for the ongoing epidemics of Zika virus (ZIKV). Here we report a non-human primate model using a 2016 contemporary clinical isolate of ZIKV. Upon subcutaneous inoculation, rhesus macaques developed fever and viremia, with robust excretion of ZIKV RNA in urine, saliva, and lacrimal fluid. Necropsy of two infected animals revealed that systematic infections involving central nervous system and visceral organs were established at the acute phrase. ZIKV initially targeted the intestinal tracts, spleen, and parotid glands, and retained in spleen and lymph nodes till 10days post infection. ZIKV-specific immune responses were readily induced in all inoculated animals. The non-human primate model described here provides a valuable platform to study ZIKV pathogenesis and to evaluate vaccine and therapeutics.
