Circulating microRNA profiles of Hendra virus infection in horses

Abstract

Hendra virus (HeV) is an emerging zoonotic pathogen harbored by Australian mainland flying foxes. HeV infection can cause lethal disease in humans and horses, and to date all cases of human HeV disease have resulted from contact with infected horses. Currently, diagnosis of acute HeV infections in horses relies on the productive phase of infection when virus shedding may occur. An assay that identifies infected horses during the preclinical phase of infection would reduce the risk of zoonotic viral transmission during management of HeV outbreaks. Having previously shown that the host microRNA (miR)-146a is upregulated in the blood of HeV-infected horses days prior to the detection of viremia, we have profiled miRNAs at the transcriptome-wide level to comprehensively assess differences between infected and uninfected horses. Next-generation sequencing and the miRDeep2 algorithm identified 742 mature miRNA transcripts corresponding to 593 miRNAs in whole blood of six horses (three HeV-infected, three uninfected). Thirty seven miRNAs were differentially expressed in infected horses, two of which were validated by qRT-PCR. This study describes a methodology for the transcriptome-wide profiling of miRNAs in whole blood and supports the notion that measuring host miRNA expression levels may aid infectious disease diagnosis in the future.

Downregulation of MicroRNA eca-mir-128 in Seminal Exosomes and Enhanced Expression of CXCL16 in the Stallion Reproductive Tract Are Associated with Long-Term Persistence of Equine Arteritis Virus

“…From a confirmative viewpoint, these findings are similar to those reported for human SEs (34), suggesting that these miRNAs can be involved in similar modulatory processes in both species. Furthermore, the let-7 family of miRNAs as well as mir-21 are highly abundant in equine serum and plasma and also expressed in diverse tissue types (59,(75)(76)(77)(78)(79)(80). Validation of the miRNA sequencing data by RT-qPCR confirmed specific downregulation of eca-mir-128 in long-term persistently infected stallions, an intronic miRNA encoded by two distinct genes, eca-mir-128-1 and eca-mir-128-2, located on (81).…”

MicroRNA Biomarkers for Infectious Diseases: From Basic Research to Biosensing

“…Instead, the degree of variation or the relationship of one miRNA to another may provide more effective differentiation between infected and noninfected individuals. Cowled et al (2017) found that using ratios of two miRNAs ( miR_A miR_B ) improved the adjusted P-values by normalizing for individual heterogeneity. Notably, these ratios were not arbitrarily selected; every possible combination of miRNAs was tested to identify those ratios that had the most statistically significant difference between groups.…”

“…This elevation was found to occur days before the detection of the viral genome. A subsequent study took an unbiased NGS-based approach to profile miRNAs within the blood of infected horses and found that 37 miRNAs were significantly altered in the blood of infected horses relative to healthy controls (Cowled et al, 2017). This study also examined the potential use of ratios of miRNAs, rather than individual abundances, to distinguish infected from uninfected animals.…”

The role of microRNAs in animal physiology and pathology

“…Upregulation of this molecule was shown in equine blood experimentally infected with HeV16. They suppose, that miRNA profiling could be used to aid early HeV disease diagnosis, but it's worth remembering that differential expression of miR-146a is induced by several pathogens, including bacteria and other viruses [92,93,[104][105][106]. Tian et al [107] found that miR-15b is a significant marker of Marek's disease virus (MDV) infection in chickens.…”