Тип публикации: статья из журнала
Год издания: 2023
Идентификатор DOI: 10.1038/s41467-023-36754-z
Ключевые слова: live attenuated vaccines, Viral immune evasion, science, humanities and social sciences, multidisciplinary
Аннотация: <jats:title>Abstract</jats:title><jats:p>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 inactivПоказать полностьюated, we show that the PLpro DUB is an important MERS-CoV interferon antagonist and virulence factor. Although the DUB-negative rMERS-CoV<jats:sub>MA</jats:sub> 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-CoV<jats:sub>MA</jats:sub> 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-CoV<jats:sub>MA</jats:sub> 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.</jats:p>
Журнал: Nature Communications
Выпуск журнала: Т. 14, № 1
Номера страниц: 1141
ISSN журнала: 20411723