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However, working safely with pathogens that have pandemic potential requires tight regulation and the use of high-level physical and biological risk mitigation strategies to stop accidental loss of containment. Here, we used a biological containment system for influenza viruses to study strains with pandemic potential. The system relies on deletion of the essential HA gene from the viral genome and its provision by a genetically modified cell line, to which virus propagation is therefore restricted. We show that this method permits safe handling of these pathogens, including gain-of-function variants, without the risk of generating fully infectious viruses. Furthermore, we demonstrate that this system can be used to assess virus sensitivity to both approved and experimental drugs, as well as the antigenic profile of viruses, important considerations for evaluating prepandemic vaccine and antiviral strategies.<\/jats:p>","DOI":"10.1128\/msphere.00423-20","type":"journal-article","created":{"date-parts":[[2020,8,25]],"date-time":"2020-08-25T13:01:12Z","timestamp":1598360472000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":17,"title":["Application of a Biologically Contained Reporter System To Study Gain-of-Function H5N1 Influenza A Viruses with Pandemic Potential"],"prefix":"10.1128","volume":"5","author":[{"given":"Eva E.","family":"Spieler","sequence":"first","affiliation":[{"name":"Institute of Medical Virology, University of Zurich, Zurich, Switzerland"},{"name":"Life Science Zurich Graduate School, ETH and University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Moritz","sequence":"additional","affiliation":[{"name":"Institute of Medical Virology, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Stertz","sequence":"additional","affiliation":[{"name":"Institute of Medical Virology, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3891-9480","authenticated-orcid":false,"given":"Benjamin G.","family":"Hale","sequence":"additional","affiliation":[{"name":"Institute of Medical Virology, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","unstructured":"WHO. 2018. 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