MicroRNAs: Mediators and Therapeutic Targets to Airway Hyper Reactivity After Respiratory Syncytial Virus Infection

Abstract

Respiratory syncytial virus (RSV) is the most important pathogen correlated to the first-time infant wheezing and later recurrence after its primary infection. RSV infection promotes the bronchial smooth muscle sensitivity to leukotrienes (LTs) in acute stage, causes the extensive inflammatory reaction and the aggregation of Th2-like cells during respiratory tract obstruction. Infants and young children infected with RSV exhibit an increased susceptibility to the exposure of exogenous allergens, easy to suffer from the recurrent wheezing, which prompts that the body is still in a state of inflammation or immunological bias. However, the pathological mechanism is unclear. The recent researches demonstrate that abnormal expression of non-coding microRNAs (miRNAs) can be detected from the peripheral blood and airway tract epithelial of RSV infected infants, which participate the regulation of immune cells polarization and LTs synthesis. Improving the immune tolerance can significantly relieve the airway inflammation and broncho-spasm caused by RSV. In this review, we discuss recent advances in understanding the mechanism of RSV-induced inflammatory reaction and immune dysfunction leading to airway hyper-reactivity. Further, we summarize the potential molecular basis that, in this process, miRNAs, which are produced by airway epithelial cells or peripheral blood mononuclear cells, directly or in the form of exosome to regulate the inflammation programs as well as the function, differentiation and proliferation of immune cells. miRNAs may become a potential bio-marker of detecting severe RSV infection and a novel target of early intervention and therapeutic strategy in recurrent wheezing or asthma related to RSV infection.

Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium

“…MicroRNAs (miRNAs) are short non-coding RNAs involved in post-transcriptional modulation of biological processes, and implicated in a number of diseases (Tan et al, 2014). miRNAs are found to be induced by viral infections and may play a role in the modulation of antiviral responses and inflammation (Gutierrez et al, 2016;Deng et al, 2017;Feng et al, 2018). In the case of chronic airway inflammatory diseases, circulating miRNA changes were found to be linked to exacerbation of the diseases (Wardzynska et al, 2020).…”

“…Conversely, miR-22 was shown to be suppressed in asthmatic epithelium in IFV infection which lead to aberrant epithelial response, contributing to exacerbations (Moheimani et al, 2018). Other than these direct evidence of miRNA changes in contributing to exacerbations, an increased number of miRNAs and other non-coding RNAs responsible for immune modulation are found to be altered following viral infections (Globinska et al, 2014;Feng et al, 2018;Hasegawa et al, 2018). Hence non-coding RNAs also presents as targets to modulate viral induced airway changes as a means of managing exacerbation of chronic airway inflammatory diseases.…”

Immunologic and Non-Immunologic Mechanisms Leading to Airway Remodeling in Asthma

“…Moreover, the above-mentioned intracellular signaling pathways can be activated by asthma relevant micro-organisms such as rhinovirus, respiratory syncytial virus (RSV), bacteria, or intracellular parasites [62][63][64][65][66]. However, we are just starting to understand the mechanisms by which these different micro-organisms activate intracellular signaling of host cells and how they use this for their own benefit.…”

“…The fact that micro-organisms activate the same signaling pathways and cytokines as other asthma triggers might explain how they stimulate airway wall remodeling [62,63]. Dependent on the host cell type, there is also evidence that for example RSV directly affect the interaction between mesenchymal cells and epithelial cells [65], and lead to airway hyper-reactivity [66]. The interaction between the tissue forming cells, also called the epithelial-mesenchymal trophic unit, is a key mechanism to understand the origin of airway wall remodeling.…”

“…Thus, a deregulated expression of HSPs might also explain steroid resistance in asthma patients. Other micro-organisms might affect airway smooth muscle cell remodeling by similar mechanisms [62,[64][65][66], but more details need to be investigated.…”