ArticleJournal of virology2019
Analysis of Coronavirus Temperature-Sensitive Mutants Reveals an Interplay between the Macrodomain and Papain-Like Protease Impacting Replication and Pathogenesis.
Article in Journal of virology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 35 citations in OpenAlex.
- Recombinant infectious bronchitis virus containing mutations in non-structural proteins 10, 14, 15, and 16 and within the macrodomain provides complete protection against homologous challenge.Journal of virology · 2025Article
- Mutation of a highly conserved isoleucine residue in loop 2 of several β-coronavirus macrodomains indicates that enhanced ADP-ribose binding is detrimental for replication.Journal of virology · 2024Article
- Abortive Infection of Animal Cells: What Goes Wrong.Annual review of virology · 2024Review
- Abortive Infection of Animal Cells: What Goes Wrong.Annual review of virology · 2024Review
- Mutation of a highly conserved isoleucine residue in loop 2 of severalbioRxiv : the preprint server for biology · 2024Article
- Deubiquitinating activity of SARS-CoV-2 papain-like protease does not influence virus replication or innate immune responses in vivo.PLoS pathogens · 2024Article
- SARS-CoV-2 Mac1 is required for IFN antagonism and efficient virus replication in cell culture and in mice.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Insight into the mechanisms of coronaviruses evading host innate immunity.Biochimica et biophysica acta. Molecular basis of disease · 2023Review
- From Immunogen to COVID-19 vaccines: Prospects for the post-pandemic era.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Review
- Article
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- A Temperature-Sensitive Recombinant of Avian Coronavirus Infectious Bronchitis Virus Provides Complete Protection against Homologous Challenge.Journal of virology · 2022Article
- A persistent high ambient temperature waned the community spread of severe acute respiratory syndrome coronavirus-2 in Pakistan.New microbes and new infections · 2022Article
- Elevated temperature inhibits SARS-CoV-2 replication in respiratory epithelium independently of IFN-mediated innate immune defenses.PLoS biology · 2021Article
- Structure of the multiple functional domains from coronavirus nonstructural protein 3.Emerging microbes & infections · 2021Article
- Could live attenuated vaccines better control COVID-19?Vaccine · 2021Review
- Unique Mutations in the Murine Hepatitis Virus Macrodomain Differentially Attenuate Virus Replication, Indicating Multiple Roles for the Macrodomain in Coronavirus Replication.Journal of virology · 2021Article
- Dissecting the novel mechanism of reduning injection in treating Coronavirus Disease 2019 (COVID-19) based on network pharmacology and experimental verification.Journal of ethnopharmacology · 2021Article
- SARS-CoV-2 transmission via aquatic food animal species or their products: A review.Aquaculture (Amsterdam, Netherlands) · 2021Article
- The Impact of Temperature on the Risk of COVID-19: A Multinational Study.International journal of environmental research and public health · 2021Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Analysis of temperature-sensitive (ts) mutant viruses is a classic method allowing researchers to identify genetic loci involved in viral replication and pathogenesis. Here, we report genetic analysis of a ts strain of mouse hepatitis virus (MHV), tsNC11, focusing on the role of mutations in the macrodomain (MAC) and the papain-like protease 2 (PLP2) domain of nonstructural protein 3 (nsp3), a component of the viral replication complex. Using MHV reverse genetics, we generated a series of mutant viruses to define the contributions of macrodomain- and PLP2-specific mutations to the ts phenotype. Viral replication kinetics and efficiency-of-plating analysis performed at permissive and nonpermissive temperatures revealed that changes in the macrodomain alone were both necessary and sufficient for the ts phenotype. Interestingly, mutations in the PLP2 domain were not responsible for the temperature sensitivity but did reduce the frequency of reversion of macrodomain mutants. Coimmunoprecipitation studies are consistent with an interaction between the macrodomain and PLP2. Expression studies of the macrodomain-PLP2 portion of nsp3 indicate that the ts mutations enhance proteasome-mediated degradation of the protein. Furthermore, we found that during virus infection, the replicase proteins containing the MAC and PLP2 mutations were more rapidly degraded at the nonpermissive temperature than were the wild-type proteins. Importantly, we show that the macrodomain and PLP2 mutant viruses trigger production of type I interferon
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