Synergistic correlation between host angiogenin and dengue virus replication.

DENV infection poses a major health concern globally and the pathophysiology relies heavily on host-cellular machinery. Although virus replication relies heavily on the host, the mechanistic details of DENV-host interaction is not fully characterized yet. Here, we are focusing on characterizing the mechanistic basis of virus-induced stress on the host cell. Specifically, we aim to characterize the role of the stress modulator ribonuclease Angiogenin during DENV infection. Our results suggested that the levels of Angiogenin are up-regulated in DENV-infected cells and the levels increase proportionately with DENV replication. Our efforts to knockdown Angiogenin using siRNA were unsuccessful in DENV-infected cells but not in mock-infected control. To further investigate the modulation between DENV replication and Angiogenin, we treated Huh7 cells with Ivermectin prior to DENV infection. Our results suggest a significant reduction in DENV replication specifically at the later stages as a consequence of Ivermectin treatment. Interestingly, Angiogenin levels were also found to be decreased proportionately. Our results suggest that Angiogenin modulation during DENV infection is important for DENV replication and pathogenesis.

Unravelling tRNA fragments in DENV pathogenesis: Insights from RNA sequencing.

Small non-coding RNAs (sncRNAs) derived from tRNAs are known as tRNA-derived small RNAs (tsRNAs). These tsRNAs are further categorized into tRNA-derived fragments (tRFs) and tRNA halves (tiRNAs), which play significant roles in the various molecular mechanisms underlying certain human diseases. However, the generation of tsRNAs and their potential roles during Dengue virus (DENV) infection is not yet known. Here, we performed small RNA sequencing to identify the generation and alterations in tsRNAs expression profiles of DENV-infected Huh7 cells. Upon DENV infection, tRNA fragmentation was found to be increased. We identified a significant number of differentially expressed tsRNAs during DENV infection. Interestingly, the 3'tRF population showed upregulation, while the i-tRF population exhibited downregulation. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed to analyze the impact of differentially expressed tsRNAs on DENV pathogenesis. Our results suggest that differentially expressed tsRNAs are involved in transcriptional regulation via RNA polymerase II promoter and metabolic pathways. Overall, our study contributes significantly to our understanding of the roles played by tsRNAs in the complex dynamics of DENV infection.

Role of non-coding RNAs in Dengue virus-host interaction.

Dengue is potentially a life-threatening arthropod-borne viral infection for which there are no known therapeutic agents till date. Early stage diagnosis of dengue infection is still lacking. Diagnosis is only made after severe manifestations and later stages of infection. Timely prognosis can prevent dengue related mortalities. The nucleic acid-based therapy has potential to emerge as a promising approach for early diagnosis and treatment of this viral infection. Many studies have been carried out suggested the regulatory role of ncRNAs thereby revealing the importance of protein-RNA and RNA-RNA interactions during infection. Various regulatory RNAs are either expressed by mammalian cells or generated by viral RNA have reported to play important roles in viral life cycle including dengue virus. Thus exploring host-virus interaction will pave the novel path for understanding the pathophysiology of febrile infection in dengue. Rapid advances in sequencing techniques along with significant developments in the field of RNA studies has made RNA therapeutics as one of the promising approaches as antiviral targets. The idea of RNA based therapies has been greatly backed by a Hepatitis C virus drug, Miravirsen which has successfully completed phase II clinical trial. In the present review, we will discuss the implications of different non-coding RNAs in dengue infection. Differential expression of small ncRNA may serve as a reliable biomarker of disease severity during different stages of infection and can also play regulatory roles in disease progression.

Regulatory roles of tRNA-derived RNA fragments in human pathophysiology.

Hundreds of tRNA genes and pseudogenes are encoded by the human genome. tRNAs are the second most abundant type of RNA in the cell. Advancement in deep-sequencing technologies have revealed the presence of abundant expression of functional tRNA-derived RNA fragments (tRFs). They are either generated from precursor (pre-)tRNA or mature tRNA. They have been found to play crucial regulatory roles during different pathological conditions. Herein, we briefly summarize the discovery and recent advances in deciphering the regulatory role played by tRFs in the pathophysiology of different human diseases.