Aedes aegypti microRNA miR-2b regulates ubiquitin-related modifier to control chikungunya virus replication

Abstract

Arboviruses that replicate in mosquitoes activate innate immune response within mosquitoes. Regulatory non-coding microRNAs (miRNA) are known to be modulated in mosquitoes during chikungunya infection. However, information about targets of these miRNAs is scant. The present study was aimed to identify and analyze targets of miRNAs that are regulated during chikungunya virus (CHIKV) replication in Aedes aegypti cells and in the mosquito. Employing next-generation sequencing technologies, we identified a total of 126 miRNAs from the Ae. aegypti cell line Aag2. Of these, 13 miRNAs were found to be regulated during CHIKV infection. Putative targets of three of the most significantly regulated miRNAs- miR-100, miR-2b and miR-989 were also analyzed using quantitative PCRs, in cell lines and in mosquitoes, to validate whether they were the targets of the miRNAs. Our study expanded the list of miRNAs known in Ae. aegypti and predicted targets for the significantly regulated miRNAs. Further analysis of some of these targets revealed that ubiquitin-related modifier is a target of miRNA miR-2b and plays a significant role in chikungunya replication.

Aedes aegypti microRNA, miR-2944b-5p interacts with 3'UTR of chikungunya virus and cellular target vps-13 to regulate viral replication

“…A recent study from our laboratory showed that the Ae . aegypti miRNA, miR-2b regulated CHIKV replication by regulating its cellular target, ubiquitin related modifier [40]. The present study additionally revealed that miR-2b bound to CHIKV 3'UTR, albeit not having much biological relevance in directly controlling CHIKV replication.…”

Role of MicroRNAs in Bone Pathology during Chikungunya Virus Infection

“…Besides having an imperative role in physiological functions, the aberrant expression of miRNAs is associated with pathogenesis of various diseases including viral infections [ 21 , 22 , 23 ]. Recently, altered expression of several miRNAs (listed in Table 1 ) has been observed during CHIKV infection [ 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ].…”

“…The upregulated miRNAs targeted genes which encodes for protein tyrosine phosphatase SHP2, ERK1/2, and ubiquitin fusion degradation protein, respectively, whereas the downregulated miRNAs targeted the gene that encodes for the 40S ribosomal protein S16. In another study, next-generation sequencing identified the altered expression of 13 miRNAs during CHIKV infection in Aag-2 cells [ 31 ]. Target prediction analysis showed aae-miR-2b targets URM and ubiquitin whereas aae-miR-100 targets CDC42 and sumo-ligase.…”

Diverse Defenses: A Perspective Comparing Dipteran Piwi-piRNA Pathways

“…In this review we raise some key questions ( Box 1 ), we primarily discuss the Piwi protein and Piwi-interacting RNA (piRNA) pathways in these two Dipteran lineages and we touch upon the endogenous small interfering RNA (endo-siRNA), a canonical branch of RNAi. Although the microRNA (miRNA) branch of the RNAi pathway critically regulates gene expression during development for all animals [ 19 , 20 ], the role of microRNAs in transposon or virus suppression in insects has been more limited to a few studies [ 21 , 22 , 23 ], or has courted controversy [ 24 , 25 , 26 ]. We refer to [ 27 ] for further reading on this topic.…”