Ingle Harshad, Kumar Sushil, Raut Ashwin Ashok, Mishra Anamika, Kulkarni Diwakar Dattatraya, Kameyama Takeshi, Takaoka Akinori, Akira Shizuo, Kumar Himanshu
Laboratory of Immunology, Department of Biological Sciences, Indian Institute of Science Education and Research, Bhopal 462066, India.
Pathogenomics Lab, OIE Reference Lab for Avian Influenza, ICAR-National Institute of High Security Animal Diseases, Bhopal 462022, India.
Sci Signal. 2015 Dec 8;8(406):ra126. doi: 10.1126/scisignal.aab3183.
MicroRNAs (miRNAs) are small noncoding RNAs that are responsible for dynamic changes in gene expression, and some regulate innate antiviral responses. Retinoic acid-inducible gene I (RIG-I) is a cytosolic sensor of viral RNA; RIG-I activation induces an antiviral immune response. We found that miR-485 of the host was produced in response to viral infection and targeted RIG-I mRNA for degradation, which led to suppression of the antiviral response and enhanced viral replication. Thus, inhibition of the expression of mir-485 markedly reduced the replication of Newcastle disease virus (NDV) and the H5N1 strain of influenza virus in mammalian cells. Unexpectedly, miR-485 also bound to the H5N1 gene PB1 (which encodes an RNA polymerase required for viral replication) in a sequence-specific manner, thereby inhibiting replication of the H5N1 virus. Furthermore, miR-485 exhibited bispecificity, targeting RIG-I in cells with a low abundance of H5N1 virus and targeting PB1 in cells with increased amounts of the H5N1 virus. These findings highlight the dual role of miR-485 in preventing spurious activation of antiviral signaling and restricting influenza virus infection.
微小RNA（miRNA）是一类小的非编码RNA，负责基因表达的动态变化，其中一些还调控先天性抗病毒反应。维甲酸诱导基因I（RIG-I）是病毒RNA的胞质传感器；RIG-I激活可诱导抗病毒免疫反应。我们发现，宿主的miR-485在病毒感染后产生，并靶向RIG-I mRNA进行降解，从而导致抗病毒反应受到抑制，病毒复制增强。因此，抑制mir-485的表达可显著降低新城疫病毒（NDV）和甲型流感病毒H5N1株在哺乳动物细胞中的复制。出乎意料的是，miR-485还以序列特异性方式与H5N1基因PB1（编码病毒复制所需的RNA聚合酶）结合，从而抑制H5N1病毒的复制。此外，miR-485表现出双特异性，在H5N1病毒丰度较低的细胞中靶向RIG-I，在H5N1病毒量增加的细胞中靶向PB1。这些发现突出了miR-485在防止抗病毒信号的虚假激活和限制流感病毒感染方面的双重作用。
