Regulation of Host Innate Immunity by Non-Coding RNAs During Dengue Virus Infection

Abstract

An estimated 3.9 billion individuals in 128 nations (about 40% of global population) are at risk of acquiring dengue virus infection. About 390 million cases of dengue are reported each year with higher prevalence in the developing world. A recent modeling-based report suggested that half of the population across the globe is at risk of dengue virus infection. In any given dengue outbreak, a percentage of infected population develops severe clinical manifestations, and this remains one of the “unsolved conundrums in dengue pathogenesis”. Although, host immunity and virus serotypes are known to modulate the infection, there are still certain underlying factors that play important roles in modulating dengue pathogenesis. Advanced genomics-based technologies have led to identification of regulatory roles of non-coding RNAs. Accumulating evidence strongly suggests that viruses and their hosts employ non-coding RNAs to modulate the outcome of infection in their own favor. The foremost ones seem to be the cellular microRNAs (miRNAs). Being the post-transcriptional regulators, miRNAs can be regarded as direct switches capable of turning “on” or “off” the viral replication process. Recently, role of long non-coding RNAs (lncRNAs) in modulating viral infections via interferon dependent or independent signaling has been recognized. Hence, we attempt to identify the “under-dog”, the non-coding RNA regulators of dengue virus infection. Such essential knowledge will enhance the understanding of dengue virus infection in holistic manner, by exposing the specific molecular targets for development of novel prophylactic, therapeutic or diagnostic strategies.

Changes of Small Non-coding RNAs by Severe Acute Respiratory Syndrome Coronavirus 2 Infection

“…They virtually participate in all biological pathways, including cell proliferation, differentiation, apoptosis, autophagy, and tissue remodeling. sncRNAs are also essential to regulate host responses to viral infections ( Choudhuri, 2010 ; Beermann et al, 2016 ; Romano et al, 2017 ; Rajput et al, 2020 ; Wu et al, 2020 ). Among sncRNAs, the most widely studied sncRNAs are microRNAs (miRNAs), which are 18–24 nt in length, carry 5′ monophosphate and 3′ hydroxyl (3′-OH) ends, and generally regulate genes via the argonaute (AGO) platform ( Schwarz et al, 2004 ; Fabian and Sonenberg, 2012 ).…”

Dynamic transcriptome analyses reveal m6A regulated immune non-coding RNAs during dengue disease progression

“…Similar results were observed when using the top-5 most correlated genes (Figure S9 and Table S7). Accumulating evidence strongly suggested that dengue viruses and their hosts employ lncRNAs to modulate the outcome of infection in their own favor [ 11 ]. These results suggested that dengue viruses selectively suppress immune responses and cell cycle pathways in the cells it infects, that may have important consequences for virus infection and transmission.…”

“…In addition to protein-coding genes, the majority of human genome is transcribed into non-coding transcripts, which play critical roles in regulating the expression of genes [ 8 ]. Several reported studies have suggested that non-coding RNAs (ncRNAs), such as microRNAs, siRNAs and long non-coding RNAs (lncRNAs) accomplish critical roles in DENV infection [ [9] , [10] , [11] ]. In particular, lncRNAs have been recognized to be associated with various biological processes and involved in diverse types of human diseases [ 12 ].…”

“…Moreover, numbers of studies have investigated the expression of lncRNAs in dengue infection and identified several lncRNAs with perturbed expression [ 9 , 13 ]. Accumulating evidence strongly suggests that DENV and their hosts employ ncRNAs to modulate the outcome of DENV infection in their own favor [ 11 ]. For example, Wang et al identified the differentially expressed lncRNAs in DENV1 and DENV2 serotypes infected L-02 cells and found that lncRNAs were implicated in transcription regulation and signal transduction [ 14 ].…”

Association of exosomal miR‐96‐5p and miR‐146a‐5p with the disease severity in dengue virus infection

“…[14][15][16][17][18] Recent studies have found that miRNAs are widely involved in the regulation of immune and inflammatory responses by regulating the expression of cytokine genes as well as platelet biogenesis and degranulation. [19][20][21][22] A detailed, comprehensive understanding of exosomal miRNAs and their involvement in DENV infection will help to decipher the disease progression mechanism. In this study, we demonstrated the miRNA composition of the exosomes released during different stages of dengue infection.…”