Polyomavirus microRNAs circulating in biological fluids during viral persistence

Abstract

Increasing evidence suggests that microRNA-mediated gene silencing, detected during exosome intercellular communication between cells, may be exploited by persistent human viruses. Recently, it has been reported that human polyomaviruses encode microRNAs that downregulate large T expression and target host factors, helping the virus to escape immune elimination. Consequently, viral microRNAs and their genetic variability may have roles in the induction of polyomavirus reactivation, the success of persistence or replication and the development of diseases. In vitro experiments have detected polyomavirus JC (JCPyV) microRNAs in exosomes obtained from cell supernatants after viral infection and showed that they can be carried into uninfected cells. JCPyV and BKPyV microRNAs have been sought in clinical samples obtained from patients with or at risk of severe polyomavirus-associated diseases and from healthy subjects. Variable expressions of JCPyV and BKPyV microRNAs circulating in blood, urine, and cerebrospinal fluid samples were found in patients who were polyomavirus DNA positive and were also observed in negative subjects. Differences in the relationship between the JCPyV and BKPyV microRNA expressions and viral DNA load have been observed. All the data point towards a potential role of polyomavirus exosome microRNAs in viral persistence and suggest that further work is warranted to define their role in viral reactivation and to identify potential new antiviral strategies targeting these viruses.

JC Virus infected choroid plexus epithelial cells produce extracellular vesicles that infect glial cells independently of the virus attachment receptor

“…Once in the brain vesicles likely play a fundamental role in transmitting the infection to other glial cells and perhaps also to neurons in the case of granule cell neuronopathy, a rare complication of JCPyV infection of the brain [43]. Extracellular vesicles are also known to carry an abundance of regulatory molecules including transcription factors and microRNAs that influence the microenvironment of target tissues [44][45][46][47][48][49][50]. The contents of EV derived from JCPyV infected CPE cells, kidney tubule epithelial cells, and primary glial cells has yet to be examined in vitro or in vivo but such studies are likely to shed significant light on the pathogenic mechanisms of JCPyV induced disease.…”

JCPyV microRNA in plasma inversely correlates with JCPyV seropositivity among long-term natalizumab-treated relapsing-remitting multiple sclerosis patients

“…Upon reactivation, increased viral replication may be accompanied by rearrangements of archetype JCPyV, involving putative alterations within the non-coding control region (NCCR). JCPyV-carrying archetype NCCR is mainly present in asymptomatic individuals whereas viral strains with rearranged NCCR forms are frequently found in patients with PML (Martelli and Giannecchini 2017). Increased transcription, DNA replication, and expression of viral gene products would allow better immune detection of infection by both innate and adaptive immune systems of the host.…”

“…Furthermore, growing evidence suggests that JCPyV miRNAs, similar to other viral miRNAs, can reside in exosomes, and that the exosomal miRNAs may have a role in viral persistence and reactivation (Martelli and Giannecchini 2017). Remarkably, these miRNAs have been detected in exosomes obtained from plasma and urine of both JCPyV-DNA positive and JCPyV-DNA negative MS patients (Giovannelli et al 2015), suggesting that these miRNAs may provide new element in identifying patients at risk of PML.…”

Steering Against Wind: A New Network of NamiRNAs and Enhancers

“…Thousands of miRNAs and their target genes have been identified in mammals, and accumulating evidence shows that miRNAs are functionally distributed in numerous kinds of organisms, such as animals, plants, and microbes [7] , [11] , [12] , [13] , [14] . Mature miRNAs interact with Argonaute (AGO) and other associated proteins to form RNA-induced silencing complex (RISC), and then bind to the 3′UTR of their target genes by complementary base-pairing, resulting in the silencing of their target genes by blocking the translation process or inducing mRNA degradation [15] .…”