SARS-CoV-2 is sensitive to type I interferon pretreatment

Kumari G. Lokugamage; Adam Hage; Craig Schindewolf; Ricardo Rajsbaum; Vineet D. Menachery

can be determined. In addition, use of type III IFN, which is predicted to have utility in the 250 respiratory tract, could offer another means for effective treatment for SARS-CoV-2. 251 . CC-BY-NC 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi. org/10.1101 org/10. /2020 In addition to treatment, the sensitivity to type I IFN may also have implications for 252 animal model development. For SARS-CoV, mouse models that recapitulate human disease 253 were developed through virus passage in immune competent mice (46). Similarly, mouse 254 models for MERS-CoV required adaptation in mice that had genetic modifications of their 255 dipeptidyl-peptidase 4 (DPP4), the receptor for 48) . However, each of these 256 MERS-CoV mouse models still retained full immune capacity. In contrast, SARS-CoV-2 257 sensitivity to type I IFN may signal the need to use an immune deficient model to develop 258 relevant disease. While initial work has suggested incompatibility to SARS-CoV-2 infection in 259 mice based on receptor usage (8), the type I IFN response may be a second major barrier that 260 needs to be overcome. Similar to the emergent Zika virus outbreak, the use of type I IFN 261 receptor knockout mice or type I IFN receptor blocking antibody may be necessary to develop a 262 useful SARS-CoV-2 animal models for therapeutic testing (49). 263