Periodic Reporting for period 1 - COV RESTRIC (Unravelling species barriers of coronaviruses)
Período documentado: 2017-05-01 hasta 2019-04-30
The precise mechanisms that allow coronaviruses to jump across species barriers still remain elusive. Therefore, studies addressing viral control mechanisms precluding transmission across species barriers are of utmost importance to ultimately contribute to the prevention of zoonotic infections.
We hypothesized that conserved restriction factors exists between different species which limit viral replication and which need to be overcome via viral evasion and adaptation strategies in order to establish a zoonotic infection. We proposed a genetic screening approach in combination with state-of-the-art technologies to identify unknown coronavirus restriction factors, restricting replication of different coronavirus variants originating from different hosts, including the highly pathogenic human SARS-CoV and MERS-CoV. We specifically aimed to identify interferon stimulated genes (ISGs) that are conserved between different species. The type I interferon (IFN) response protects cells from viral infection by inducing hundreds of ISGs, some of which encode direct antiviral effectors that could act as viral restriction factors.
Upon application of an ISG screening approach we could identify a novel ISG, namely lymphocyte antigen 6 complex, locus E (LY6E) that potently restricts human CoVs (Figure 1). We analyzed its mechanism of action and further characterized the role of this ISG in the CoV replication cycle. In conclusion, we provide novel knowledge about innate CoV restriction factors. A deeper understanding of viral restriction could in the end lead to novel therapeutic options against emerging CoVs.
We disseminated the results of our research through different channels. We are currently preparing a manuscript for publication (Pfaender et. al. manuscript in preparation) in a high impact scientific journal. Furthermore, data has been shared at international conferences including the 29th Annual Meeting of the Society for Virology (Düsseldorf, Germany, oral presentation, abstract ID 132), the Positive Strand RNA Virus Meeting (Keystone Meeting, Killarney, Ireland; poster presentation, abstract ID 3058) and the European Congress of Virology Meeting 2019 (Rotterdam, Netherlands, poster presentation, abstract ID. 139). In addition, dissemination has been realized upon presentation of the data in internal seminars including regular progress reports and internal symposia.
With respect to Article 28 of the H2020 annotated model grant agreement, measures were taken to ensure exploitation of the research results. On the one hand, results will be exploited for future research. A “hit list” of possible candidate genes restricting coronavirus replication has been obtained which can be used for diverse follow up projects. Due to time limitations, we were not able to conduct a detailed analysis of the mechanism of action for our top hit but aim to address this question in future studies.