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- W4322626101 abstract "Coronaviruses express a papain-like protease (PLpro) that is required for replicase polyprotein maturation and also serves as a deubiquitinating enzyme (DUB). In this study, using a Middle East respiratory syndrome virus (MERS-CoV) PLpro modified virus in which the DUB is selectively inactivated, we show that the PLpro DUB is an important MERS-CoV interferon antagonist and virulence factor. Although the DUB-negative rMERS-CoVMA replicates robustly in the lungs of human dipeptidyl peptidase 4 knock-in (hDPP4 KI) mice, it does not cause clinical symptoms. Interestingly, a single intranasal vaccination with DUB-negative rMERS-CoVMA induces strong and sustained neutralizing antibody responses and sterilizing immunity after a lethal wt virus challenge. The survival of naïve animals also significantly increases when sera from animals vaccinated with the DUB-negative rMERS-CoVMA are passively transferred, prior to receiving a lethal virus dose. These data demonstrate that DUB-negative coronaviruses could be the basis of effective modified live attenuated vaccines." @default.
- W4322626101 created "2023-03-01" @default.
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- W4322626101 date "2023-02-28" @default.
- W4322626101 modified "2023-09-25" @default.
- W4322626101 title "Engineering potent live attenuated coronavirus vaccines by targeted inactivation of the immune evasive viral deubiquitinase" @default.
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- W4322626101 doi "https://doi.org/10.1038/s41467-023-36754-z" @default.
- W4322626101 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36854765" @default.
- W4322626101 hasPublicationYear "2023" @default.
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