Ebola Virus Produces Discrete Small Noncoding RNAs Independently of the Host MicroRNA Pathway Which Lack RNA Interference Activity in Bat and Human Cells

Abstract

The question as to whether RNA viruses produce bona fide microRNAs (miRNAs) during infection has been the focus of intense research and debate. Recently, several groups using computational prediction methods have independently reported possible miRNA candidates produced by Ebola virus (EBOV). Additionally, efforts to detect these predicted RNA products in samples from infected animals and humans have produced positive results. However, these studies and their conclusions are predicated on the assumption that these RNA products are actually processed through, and function within, the miRNA pathway. In the present study, we performed the first rigorous assessment of the ability of filoviruses to produce miRNA products during infection of both human and bat cells. Using next-generation sequencing, we detected several candidate miRNAs from both EBOV and the closely related Marburg virus (MARV). Focusing our validation efforts on EBOV, we found evidence contrary to the idea that these small RNA products function as miRNAs. The results of our study are important because they highlight the potential pitfalls of relying on computational methods alone for virus miRNA discovery. IMPORTANCE Here, we report the discovery, via deep sequencing, of numerous noncoding RNAs (ncRNAs) derived from both EBOV and MARV during infection of both bat and human cell lines. In addition to identifying several novel ncRNAs from both viruses, we identified two EBOV ncRNAs in our sequencing data that were near-matches to computationally predicted viral miRNAs reported in the literature. Using molecular and immunological techniques, we assessed the potential of EBOV ncRNAs to function as viral miRNAs. Importantly, we found little evidence supporting this hypothesis. Our work is significant because it represents the first rigorous assessment of the potential for EBOV to encode viral miRNAs and provides evidence contrary to the existing paradigm regarding the biological role of computationally predicted EBOV ncRNAs. Moreover, our work highlights further avenues of research regarding the nature and function of EBOV ncRNAs.

Can melatonin reduce the severity of COVID-19 pandemic?

“…À 160 pg/ ml, 7-11 y.o. À 100-110 pg/ml, [11][12][13][14][15] 3 pg/ml. The age-related changes in melatonin levels were observed during the nightly production of melatonin only.…”

“…The origins of bats' coronaviruses and factors of viral pathogenesis [9][10][11] are only partially understood. Mechanisms of anti-viral resistance in bats are understood even less, remaining mostly on the level of hypothesis [8,12,13]. SARS-CoV-2 is 96% identical to another bat's coronavirus Bat-SARSr-CoV RaTG13 [14].…”

Can Melatonin Reduce the Severity of COVID-19 Pandemic?

“…The origins of bats' coronaviruses and factors of viral pathogenesis [9,10,11] are only partially understood. Mechanisms of anti-viral resistance in bats are understood even less, remaining mostly on the level of hypothesis [12,13,14]. SARS-CoV-2 is 96% identical to another bat's coronavirus Bat-SARSr-CoV RaTG13 [15].…”

Computationally predicted SARS-COV-2 encoded microRNAs target NFKB, JAK/STAT and TGFB signaling pathways

“…Results obtained in the studies conducted after 2003 SARS and 2014 Ebola virus outbreaks showed that viral small non-coding RNA molecules are involved in pathogenesis of the disease ( Morales et al, 2017 ; Prasad et al, 2019 ; Teng et al, 2015 ). Discovering these RNA molecules may help to understand virus-host interactions during infection that could speed up effective treatment of SARS-CoV-2 caused COVID-19.…”