Cross Talk between MicroRNAs and Dengue Virus.

Dengue fever (DF) is an endemic infectious tropical disease and is rapidly becoming a global problem. Dengue fever is caused by one of the four dengue virus (DENV) serotypes and is spread by the female Aedes mosquito. Clinical manifestations of DF may range from asymptomatic to life-threatening severe illness with conditions of hemorrhagic fever and shock. Early and precise diagnosis is vital to avoid mortality from DF. A different approach is required to combat DF because of the challenges with the vaccines currently available, which are nonspecific; each is capable of causing cross-reaction and disease-enhancing antibody responses against the residual serotypes. MicroRNAs (miRNAs) are known to be implicated in DENV infection and are postulated to be involved in most of the host responses. Thus, they might be a suitable target for new strategies against the disease. The involvement of miRNAs in cellular activities and pathways during viral infections has been explored under numerous conditions. Interestingly, miRNAs have also been shown to be involved in viral replication. In this review, we summarize the role of known miRNAs, specifically the role of miRNA Let-7c (miR-Let-7c), miR-133a, miR-30e, and miR-146a, in the regulation of DENV replication and their possible effects on the initial immune reaction.

The Putative Roles and Functions of Indel, Repetition and Duplication Events in Alphavirus Non-Structural Protein 3 Hypervariable Domain (nsP3 HVD) in Evolution, Viability and Re-Emergence.

Alphavirus non-structural proteins 1-4 (nsP1, nsP2, nsP3, and nsP4) are known to be crucial for alphavirus RNA replication and translation. To date, nsP3 has been demonstrated to mediate many virus-host protein-protein interactions in several fundamental alphavirus mechanisms, particularly during the early stages of replication. However, the molecular pathways and proteins networks underlying these mechanisms remain poorly described. This is due to the low genetic sequence homology of the nsP3 protein among the alphavirus species, especially at its 3' C-terminal domain, the hypervariable domain (HVD). Moreover, the nsP3 HVD is almost or completely intrinsically disordered and has a poor ability to form secondary structures. Evolution in the nsP3 HVD region allows the alphavirus to adapt to vertebrate and insect hosts. This review focuses on the putative roles and functions of indel, repetition, and duplication events that have occurred in the alphavirus nsP3 HVD, including characterization of the differences and their implications for specificity in the context of virus-host interactions in fundamental alphavirus mechanisms, which have thus directly facilitated the evolution, adaptation, viability, and re-emergence of these viruses.