Identification Of Mi Rnas In Macaques And Differential Expression Profiling In B Cells Of SIV Infected Macaques

In the early stage of HIV infection,with the massive replication of the virus,not only the number of helper T cells dropped sharply,but also the number of B cells decreased and its function was damaged.Studies have pointed out that the state of B cells in the early stage of HIV infection can affect the immune response of the body in the later stage of infection.It can be seen that studying the immune activity of B cells in the early stage of infection is very important to understand the body's immune protection mechanism.However,the mechanism of B cell damage in the early stage of HIV infection is not very clear.miRNA is a new level of regulation of cell life activities.Therefore,analysis from the perspective of miRNA can provide clues for understanding the mechanism of B cell function impairment.Since the number of cases of early HIV infection patients is extremely small,the use of model animals facilitates research.The macaque model of SIV infection has a clinical phenotype similar to that of HIV-1 patients,and is currently the best animal model for studying the pathogenesis of AIDS and evaluating the efficacy of vaccines and drugs.In view of the fact that research on the characteristics of macaque miRNAs and the regulation of SIV replication by macaque miRNAs is rare,this study first used a combination of homology search and RNA sequencing to analyze the types and gene distribution characteristics of conserved miRNAs in the macaque genome,and compared the macaque miRNA with human miRNA and explored the evolutionary laws of miRNA genes.In this study,a total of 1558 conserved miRNA genes were identified in rhesus monkeys,of which 1413 were conserved in the genomes of cynomolgus and rhesus monkeys.There were 1083 and 1150 human miRNA precursor sequences found in the genomes of cynomolgus monkey and rhesus monkey respectively,indicating that most miRNAs were conserved during evolution.miRNA genes were mainly distributed in intergenic and intron regions,and miRNA gene clusters were widespread.Most miRNA gene clusters were conserved between humans and macaques.RNA sequencing results showed that the relative expression of miRNA was related to the evolutionary age,and the older miRNA molecules had higher expression levels.Furthermore,three SIVmac239 infected peripheral blood B cells of Chinese rhesus monkeys were isolated,and the changes in B cell miRNA expression profiles at 0,7 and 28 days after infection were compared,and the edge R package was used to screen for differentially expressed miRNAs.The results showed that the expression profile of miRNA was significantly different before and after infection.After being stimulated by SIV virus,the expression of most miRNA was up-regulated.There was little difference in miRNA expression profiles between 7 days and 28 days after infection.Most miRNAs continued to be up-regulated at 28 days after infection.Furthermore,GO and KEGG were used to predict the function of the differentially expressed miRNAs.The results suggested that the top three pathways of up-regulated miRNA target enrichment are: MAPK,Ras,and Proteoglycans in cancer;the first three pathways of down-regulated miRNA target enrichment are: MAPK,Endocytosis,Axon guidance pathways.And partially differentially expressed miRNAs could affect the activation,proliferation and differentiation of B cells through NF-?B signaling pathway,PI3K-Akt signaling pathway,and apoptosis pathway.The results of this study provided clues for understanding the effect of miRNA on B cell damage in the early stage of SIV infection.