ArticleJournal of virology2014
Virulence-associated genome mutations of murine rotavirus identified by alternating serial passages in mice and cell cultures.
Article in Journal of virology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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
22 citing papers in PubMed, 34 citations in OpenAlex.
- Article
- Cell Culture Adaptation of Porcine Group A Rotavirus: Advances and Challenges for Vaccine Development.Viruses · 2026Review
- Accumulation of mutations in nsp4, E, and the S2 subunit underlies mammalian cell tropism expansion and virulence attenuation of avian coronavirus.PLoS pathogens · 2026Article
- Mutations of two amino acids in VP5 mediate the attenuation of human rotavirus vaccine: evidence fromJournal of virology · 2025Article
- TREM-1 Interacts with Rotavirus Proteins and Drives Inflammatory Responses: A Combined Experimental and Computational Approach.Pathogens (Basel, Switzerland) · 2025Article
- Human Rotaviruses of Multiple Genotypes Acquire Conserved VP4 Mutations during Serial Passage.Viruses · 2024Article
- Article
- Establishment of a reverse genetics system for an epidemic strain of porcine rotavirus JXAY01 type G5P[23]I12.Frontiers in veterinary science · 2024Article
- Development and evaluation of an inactivated coxsackievirus A16 vaccine in gerbils.Emerging microbes & infections · 2022Article
- Review
- The Intrapopulation Genetic Diversity of RNA Virus May Influence the Sensitivity of Chlorine Disinfection.Frontiers in microbiology · 2022Article
- Review
- Comparative genomic analysis of genogroup 1 and genogroup 2 rotaviruses circulating in seven US cities, 2014-2016.Virus evolution · 2021Article
- Bottleneck Size-Dependent Changes in the Genetic Diversity and Specific Growth Rate of a Rotavirus A Strain.Journal of virology · 2020Article
- Article
- High prevalence of DS-1-like rotavirus infection in Thai adults between 2016 and 2019.PloS one · 2020Article
- An infant with acute gastroenteritis caused by a secondary infection with a Rotarix-derived strain.European journal of pediatrics · 2017Article
- Phenotypic shift inProceedings. Biological sciences · 2017Article
- Clinical and Molecular Characteristics of Human Rotavirus G8P[8] Outbreak Strain, Japan, 2014.Emerging infectious diseases · 2017Article
- Human G3P[9] rotavirus strains possessing an identical genotype constellation to AU-1 isolated at high prevalence in Brazil, 1997-1999.The Journal of general virology · 2015Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
unlabelledAlthough significant clinical efficacy and safety of rotavirus vaccines were recently revealed in many countries, the mechanism of their attenuation is not well understood. We passaged serially a cell culture-adapted murine rotavirus EB strain in mouse pups or in cell cultures alternately and repeatedly and fully sequenced all 11 genes of 21 virus samples passaged in mice or in cell cultures. Sequence analysis revealed that mouse-passaged viruses that regained virulence almost consistently acquired four kinds of amino acid (aa) substitutions in VP4 and substitution in aa 37 (Val to Ala) in NSP4. In addition, they gained and invariably conserved the 3' consensus sequence in NSP1. The molecular changes occurred along with the acquisition of virulence during passages in mice and then disappeared following passages in cell cultures. Intraperitoneal injection of recombinant NSP4 proteins confirmed the aa 37 site as important for its diarrheagenic activity in mice. These genome changes are likely to be correlated with rotavirus virulence. IMPORTANCE: Serial passage of a virulent wild-type virus in vitro often results in loss of virulence of the virus in an original animal host, while serial passage of a cell culture-adapted avirulent virus in vivo often gains virulence in an animal host. Actually, live attenuated virus vaccines were originally produced by serial passage in cell cultures. Although clinical efficacy and safety of rotavirus vaccines were recently revealed, the mechanism of their attenuation is not well understood. We passaged serially a murine rotavirus by alternating switch of host (mice or cell cultures) repeatedly and sequenced the eleven genes of the passaged viruses to identify mutations associated with the emergence or disappearance of virulence. Sequence analysis revealed that changes in three genes (VP4, NSP1, and NSP4) were associated with virulence in mice. Intraperitoneal injection of recombinant NSP4 proteins confirmed its diarrheagenic activity in mice. These genome changes are likely to be correlated with rotavirus virulence.
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