In recent years, the seasonal influenza occurs frequently, and avian influenza viruses, especially H7N9 and highly pathogenic virus H5N1, infect people occasionally with the capability for interspecies transmission. This exerts a public health threat and an extensive economic burden on a global scale. At present, there is no effective treatment for influenza virus infection. Given the frequent outbreaks of influenza viruses in the past two years, it is particularly urgent to develop effective ways to suppress influenza virus infection.
MicroRNAs play an important role in the post-transcriptional regulation of genes in the infection and replication of influenza viruses. Prof. MENG Songdong’s lab and Prof. FANG Min’s lab, from Institute of Microbiology, Chinese Academy of Sciences (IMCAS), found that the vast majority of endogenous cellular miRNAs from epithelial cells suppressed influenza virus replication.
They systematically screened 297 cellular miRNAs from human and mouse epithelial cells and identified five inhibitory miRNAs that efficiently inhibited influenza virus replication in vitro and in vivo.
In the further study of the remarkably inhibitory miRNAs, they found that these microRNAs could suppress viral replication, either by directly targeting at least one viral mRNAs of influenza viruses, or by targeting a supportive host factor ATP6V1A.
Moreover, Treatment with a combination of the five miRNAs through agomir delivery pronouncedly suppressed viral replication and effectively improved protection against lethal challenge with PR8 in mice.
What’s importantly, by analyzing viral gene sequences of the avian flu, swine flu, and human flu viruses, they found that the number of miRNA binding sites in viral RNA segments was positively associated with the activity of host miRNA-induced antiviral defense.
These data suggest that the highly expressed miRNAs in respiratory epithelial cells elicit effective antiviral defenses against influenza A viruses and will be useful for designing miRNA-based therapies against viral infection.
The result of this study was published online in Molecular Therapy - Nucleic Acids
(https://www.sciencedirect.com/science/article/pii/S2162253117303177), entitled Endogenous Cellular microRNAs Mediate Antiviral Defense against state-run Influenza A Virus. Dr. PENG Shanxin from MENG’s lab and Dr. WANG Jing from FANG Min’s lab are the co-authors of the study, and Prof. MENG and Prof. FANG are the co-authors.
This work is supported by the funding from Major State Basic Research Development Program of China, National Natural Science Foundation of China, and Strategic Priority Research Program of the Chinese Academy of Sciences.
Contact:
MENG Songdong, FANG Min
CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
E-mail: mengsd@im.ac.cn, fangm@im.ac.cn
Abstract:
MicroRNAs play an important role in the post-transcriptional regulation of genes in the infection and replication of influenza viruses. Prof. MENG Songdong’s lab and Prof. FANG Min’s lab, from Institute of Microbiology, Chinese Academy of Sciences (IMCAS), found that the vast majority of endogenous cellular miRNAs from epithelial cells suppressed influenza virus replication.
Key words:
influenza viruses, MicroRNAs, supress
Research