Author: Xufang Deng; Yafang Chen; Anna M. Mielech; Matthew Hackbart; Kristina R. Kesely; Robert C. Mettelman; Amornrat O’Brien; Mackenzie E. Chapman; Andrew D. Mesecar; Susan C. Baker
Title: Structure-Guided Mutagenesis Alters Deubiquitinating Activity and Attenuates Pathogenesis of a Murine Coronavirus Document date: 2019_9_25
ID: l3qp0n9f_11
Snippet: The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/782409 doi: bioRxiv preprint (D1772A), we found that the DUB activity of PLP2 was greatly reduced and a recombinant MHV 219 carrying this mutation (DUBmut) activated an earlier IFN response in macrophages. Although we 220 only observed a subtle attenuation of the DUBmut virus in the tested animal models, we 221 demonstrated that PL.....
Document: The copyright holder for this preprint (which was not peer-reviewed) is the author/funder. . https://doi.org/10.1101/782409 doi: bioRxiv preprint (D1772A), we found that the DUB activity of PLP2 was greatly reduced and a recombinant MHV 219 carrying this mutation (DUBmut) activated an earlier IFN response in macrophages. Although we 220 only observed a subtle attenuation of the DUBmut virus in the tested animal models, we 221 demonstrated that PLP2 DUB activity does play a role in suppressing the host immune response 222 and is a virulence trait, strengthening our earlier discoveries on SARS-CoV PLpro (4). We further 223 investigated the differences in the interferon response generated in response to WT versus 224 DUBmut virus in our companion study (Volk et al., submitted) , which further supports a role for 225 DUB activity in modulating the interferon response in macrophages.
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