RNA viruses can hijack vertebrate microRNAs to suppress innate immunity

Here it is proposed that RNA viruses can adapt to use the antiviral properties of microRNAs to limit viral replication and suppress innate immunity in particular cell types, and this restriction can lead to exacerbation of disease severity. RNA virus hijacks miRNAs to suppress immunity This paper reports a novel interaction between a haematopoietic-cell-specific microRNA (miRNA) and the eastern equine encephalitis virus (EEEV), an RNA virus that can be transmitted to humans via a mosquito vector. Infected humans show limited symptoms initially but can go on to develop a potentially lethal brain infection. Using a mouse model, the authors show that miR-142-3p restricts the replication of EEEV in myeloid cells through a specific interaction with the 3' non-translated region of the virus. But this antiviral action at the same time limits the induction of innate immunity and then favours viral replication, exacerbating the disease. Currently, there is little evidence for a notable role of the vertebrate microRNA (miRNA) system in the pathogenesis of RNA viruses.sup.1. This is primarily attributed to the ease with which these viruses mutate to disrupt recognition and growth suppression by host miRNAs.sup.2,3. Here we report that the haematopoietic-cell-specific miRNA miR-142-3p potently restricts the replication of the mosquito-borne North American eastern equine encephalitis virus in myeloid-lineage cells by binding to sites in the 3' non-translated region of its RNA genome. However, by limiting myeloid cell tropism and consequent innate immunity induction, this restriction directly promotes neurologic disease manifestations characteristic of eastern equine encephalitis virus infection in humans. Furthermore, the region containing the miR-142-3p binding sites is essential for efficient virus infection of mosquito vectors. We propose that RNA viruses can adapt to use antiviral properties of vertebrate miRNAs to limit replication in particular cell types and that this restriction can lead to exacerbation of disease severity.
Author(s): Derek W. Trobaugh [sup.1] , Christina L. Gardner [sup.1] , Chengqun Sun [sup.1] , Andrew D. Haddow [sup.2] , Eryu Wang [sup.2] , Elik Chapnik [sup.3] , Alexander Mildner [...]