ArticleJournal of virology2005
Single-amino-acid substitutions in open reading frame (ORF) 1b-nsp14 and ORF 2a proteins of the coronavirus mouse hepatitis virus are attenuating in mice.
Article in Journal of virology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 98 citations in OpenAlex.
- The Reassessed Potential of SARS-CoV-2 Attenuation for COVID-19 Vaccine Development-A Systematic Review.Viruses · 2022Pooled it
- Characteristics of an emerging canine respiratory coronavirus in China.The veterinary quarterly · 2025Article
- A structural roadmap for the formation of the coronavirus nsp3/nsp4 double membrane vesicle pore and its implications for polyprotein processing and replication/transcription.Journal of virology · 2025Article
- Recurrent viral capture of cellular phosphodiesterases that antagonize OAS-RNase L.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Virus hijacking of host epigenetic machinery to impair immune response.Journal of virology · 2023Review
- Recurrent Viral Capture of Cellular Phosphodiesterases that Antagonize OAS-RNase L.bioRxiv : the preprint server for biology · 2023Article
- Classification, replication, and transcription ofFrontiers in microbiology · 2023Review
- Synthetic Platforms for Characterizing and Targeting of SARS-CoV-2 Genome Capping Enzymes.ACS synthetic biology · 2022Article
- Identification of Amino Acids within Nonstructural Proteins 10 and 14 of the Avian Coronavirus Infectious Bronchitis Virus That Result in AttenuationJournal of virology · 2022Article
- Article
- Mechanisms of Coronavirus Genome Stability As Potential Targets for Antiviral Drugs.Herald of the Russian Academy of Sciences · 2022Article
- Structure-function analysis of the nsp14 N7-guanine methyltransferase reveals an essential role inProceedings of the National Academy of Sciences of the United States of America · 2021Article
- Characteristics of viral specimens collected from asymptomatic and fatal cases of COVID-19.Journal of biomedical research · 2020Article
- Infectious Bronchitis Virus Evolution, Diagnosis and Control.Veterinary sciences · 2020Review
- Effects of hypervariable regions in spike protein on pathogenicity, tropism, and serotypes of infectious bronchitis virus.Virus research · 2018Article
- A novel mechanism of RNase L inhibition: Theiler's virus L* protein prevents 2-5A from binding to RNase L.PLoS pathogens · 2018Article
- Lineage A Betacoronavirus NS2 Proteins and the Homologous Torovirus Berne pp1a Carboxy-Terminal Domain Are Phosphodiesterases That Antagonize Activation of RNase L.Journal of virology · 2017Article
- Epigenetic Landscape during Coronavirus Infection.Pathogens (Basel, Switzerland) · 2017Article
- The Golgi associated ERI3 is a Flavivirus host factor.Scientific reports · 2016Article
- Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
A reverse genetic system was recently established for the coronavirus mouse hepatitis virus strain A59 (MHV-A59), in which cDNA fragments of the RNA genome are assembled in vitro into a full-length genome cDNA, followed by electroporation of in vitro-transcribed genome RNA into cells with recovery of viable virus. The "in vitro-assembled" wild-type MHV-A59 virus (icMHV-A59) demonstrated replication identical to laboratory strains of MHV-A59 in tissue culture; however, icMHV-A59 was avirulent following intracranial inoculation of C57BL/6 mice. Sequencing of the cloned genome cDNA fragments identified two single-nucleotide mutations in cloned genome fragment F, encoding a Tyr6398His substitution in open reading frame (ORF) 1b p59-nsp14 and a Leu94Pro substitution in the ORF 2a 30-kDa protein. The mutations were repaired individually and together in recombinant viruses, all of which demonstrated wild-type replication in tissue culture. Following intracranial inoculation of mice, the viruses encoding Tyr6398His/Leu94Pro substitutions and the Tyr6398His substitution alone demonstrated log10 50% lethal dose (LD50) values too great to be measured. The Leu94Pro mutant virus had reduced but measurable log10 LD5), and the "corrected" Tyr6398/Leu94 virus had a log10 LD50 identical to wild-type MHV-A59. The experiments have defined residues in ORF 1b and ORF 2a that attenuate virus replication and virulence in mice but do not affect in vitro replication. The results suggest that these proteins serve roles in pathogenesis or virus survival in vivo distinct from functions in virus replication. The study also demonstrates the usefulness of the reverse genetic system to confirm the role of residues or proteins in coronavirus replication and pathogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.