Research On Host Interactions With Ebola Virus And Influenza A Virus At MicroRNA Level

RNA virus contains many species, such as Ebola virus, influenza virus, the Middle East respiratory syndrome coronavirus and dengue virus. In recent years, outbreak and prevalence of these viruses have been a serious threat to human health, particularly the recent outbreak of Ebola virus in West Africa, which caused the death rate reaches 40%. During RNA virus infection, virus and host can utilize different approaches to defense each other, and one of them is microRNA. MicroRNA as a class of small RNA fragment plays an important role in gene regulation. One specific microRNA can regulate hundreds of genes expression, and this high efficient regulation mechanism can be used by virus to assist its infection. Although it is known that microRNA participate in the process of virus infection, the specific mechanism under Infection is still unclear.In order to study the function of microRNA during RNA virus infection, Ebola virus and influenza virus have been chosen to analyze, respectively. In Ebola virus, the genome sequences were analyzed by bioinformatic methods and one microRNA coding sequence has been found. In addition, published RNA-Seq sequencing data which obtained from Ebola virus infected patients serum were used to verify the predicted sequences. Combined with in vitro experiments, we found that the predicted sequence could encode a real microRNA and named as Zebov-miR-1-5p. This microRNA is similar to human endogenous microRNA has-miR-155-5p, and inhibits KPNA1 expression, which is an important cofactor regulate the nuclear translocation of STAT1 and downstream signal transduction. Ebola virus hijacks this pathway by microRNA to repress the interferon signal and ultimately escape from the host immune surveillance. In contrast, even though influenza virus does not encode any viral microRNA, part of host microRNAs will gradually decreased along with virus replication. Luciferase reporter assay results showed that miR-23a, whose expression was decreased after influenza virus infection, can target partial sequence of the virus polymerase genes. This result indicated that the replication rate of influenza virus can be suppressed in host cells. According to these functions of miR-23a, supplement synthesized miR-23a directly into blood could improve the influenza virus infection outcome in a mouse model.Taken together, we concluded that individual RNA virus may exploit different approaches to against the host, including coding microRNAs to escape immune surveillance or utilize host microRNAs to control their replication and infection cycle. Therefore, different strategies have been used at microRNA level, RNA virus use these specific strategies to sustain a balance between amplification and spreading in the host during infection. Sufficient study on interactions between different virus and host is very important for new drugs screening and clinic therapy.