Since miR-484 and miR-744 overexpression suppresses DENV-2 protein production such as NS1, we suggest that both miRNAs might affect DENV replication, but simultaneously, DENV infection decreases the expression of miR-744 and miR-484. Although the mechanisms through which miR-484 and miR-744 inhibit DENV replication remain uncertain, the DENV 3′ UTR is known to contain conserved sequences involved in viral RNA circularisation and host-protein interaction. Consequently, such an effect might be associated with interference in these events. For example, PTB is reported to interact with the 3′ UTR of DENV RNA and is required for efficient DENV propagation in Vero cells (de Nova-Ocampo et al. 2002). Furthermore, we recently reported that miR-133a inhibits DENV replication by decreasing PTB expression (Castillo et al. 2016), a direct and functional target of miR-133a. Interestingly, the target sites of miR-133a, miR-484, and miR-744 are located in a single region, highlighting a ‘hotspot’ of potential MRE. The interaction of these miRNAs with the 3′ UTR of DENV RNA might lead to failure in the recruitment of PTB, thus affecting the circularisation of the viral genome, with consequences on virus replication or RNA translation. Our data are consistent with those of a previous report showing that cellular miRNAs suppress/inhibit DENV replication (Wen et al. 2015). Furthermore, antisense oligomers or small interfering RNAs directed against target sequences in the 3′ UTR of DENV RNA are also known to inhibit virus replication and translation, presumably by blocking either the RNA-RNA interactions by steric interference, or the RNA-protein interaction complexes involved in the synthesis or translation of viral RNA (Holden et al. 2006). Similar results were observed using a related strategy for the avian leucosis virus subgroup J (ALV-J) (Wang et al. 2013), where the authors showed that the activity of the luciferase-reporter gene carrying the 5′ and 3′ UTR of ALV-J decreased with the host-encoded gga-miR-1650 that interacts with the 5′ UTR. The demonstration that host miR-484 and miR-744 share a target site in the 3′ UTR of the RNA in all four DENV serotypes suggests that these miRNAs might be part of the host antiviral response against DENV. However, it is necessary to emphasize that the anti-DENV activity of miR-744 was much stronger compared to the activity observed with miR-744. Notably, this is an unexpected result since both miRNAs share some degree of sequence homology, although the miR-484 seed region shares complete homology with the 3′ UTR of the DENV recognition site. In line with our results, Wu et al. (2014) also recently reported that DENV-2 infection decreases miR-223 expression in Vero cells, but that overexpression of miR-223 suppresses DENV-2 replication, suggesting that miR-223 may be present as an antiviral factor against DENV-2. Furthermore, our results gain importance because miR-744 was reported to direct the post-transcriptional regulation of TGF-β1, which is crucial in inflammation (Martin et al. 2011), and this cytokine is reported to be involved in severe dengue disease (Chen et al. 2009). In addition, a large body of evidence has indicated that TGF-β1 gene polymorphisms are associated with increased susceptibility to dengue haemorrhagic fever and higher virus load, and high TGF-β1 production has been linked to protection or a mild clinical outcome of dengue infection (Chen et al. 2009).