ArticlePLoS pathogens2011
Norovirus regulation of the innate immune response and apoptosis occurs via the product of the alternative open reading frame 4.
Article in PLoS pathogens, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
146 citing papers in PubMed, 1 synthesis or guideline pooled it, 235 citations in OpenAlex.
- Pooled it
- Norovirus in symptomatic and asymptomatic individuals: cytokines and viral shedding.Clinical and experimental immunology · 2016Trial
- Article
- Balancing under constraint: Structural insights into norovirus evolution and antigenic innovation.PLoS pathogens · 2026Article
- The MNV-1 protease-polymerase precursor cleaves a novel site in the NS1-2 protein.The Journal of general virology · 2026Article
- Clinical and Epidemiological Features of Calicivirus Infections in Cattle.Animals : an open access journal from MDPI · 2026Review
- Proof of concept: targeted protein degradation of the stress granules component G3BP1 as an antiviral strategy against norovirus infection.Antimicrobial agents and chemotherapy · 2026Article
- Mechanisms of Norovirus Immunity: Implications for Vaccine Design.Annual review of pathology · 2026Review
- Article
- iPLA2β-null mice exposed to natural pathogens exhibit hepatocellular fibrotic injury with male-biased alteration of glycerolipid metabolism.Frontiers in immunology · 2026Article
- TRIM47 inhibits murine norovirus replication in a strain-dependent manner.Journal of virology · 2025Article
- Egress-enhancing mutation reveals the inefficiency of non-enveloped virus cell exit.PLoS biology · 2025Article
- Genomic diversity and comparative phylogenomic analysis of genus Norovirus.Scientific reports · 2025Article
- Translation of Overlapping Open Reading Frames Promoted by Type 2 IRESs in Avian Calicivirus Genomes.Viruses · 2024Article
- Norovirus-mediated translation repression promotes macrophage cell death.PLoS pathogens · 2024Article
- The Disorderly Nature of Caliciviruses.Viruses · 2024Review
- A narrative review of norovirus epidemiology, biology, and challenges to vaccine development.NPJ vaccines · 2024Review
- Noroviruses: Evolutionary Dynamics, Epidemiology, Pathogenesis, and Vaccine Advances-A Comprehensive Review.Vaccines · 2024Review
- Highs and Lows in Calicivirus Reverse Genetics.Viruses · 2024Review
- Human norovirus cultivation systems and their use in antiviral research.Journal of virology · 2024Review
86 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Small RNA viruses have evolved many mechanisms to increase the capacity of their short genomes. Here we describe the identification and characterization of a novel open reading frame (ORF4) encoded by the murine norovirus (MNV) subgenomic RNA, in an alternative reading frame overlapping the VP1 coding region. ORF4 is translated during virus infection and the resultant protein localizes predominantly to the mitochondria. Using reverse genetics we demonstrated that expression of ORF4 is not required for virus replication in tissue culture but its loss results in a fitness cost since viruses lacking the ability to express ORF4 restore expression upon repeated passage in tissue culture. Functional analysis indicated that the protein produced from ORF4 antagonizes the innate immune response to infection by delaying the upregulation of a number of cellular genes activated by the innate pathway, including IFN-Beta. Apoptosis in the RAW264.7 macrophage cell line was also increased during virus infection in the absence of ORF4 expression. In vivo analysis of the WT and mutant virus lacking the ability to express ORF4 demonstrated an important role for ORF4 expression in infection and virulence. STAT1-/- mice infected with a virus lacking the ability to express ORF4 showed a delay in the onset of clinical signs when compared to mice infected with WT virus. Quantitative PCR and histopathological analysis of samples from these infected mice demonstrated that infection with a virus not expressing ORF4 results in a delayed infection in this system. In light of these findings we propose the name virulence factor 1, VF1 for this protein. The identification of VF1 represents the first characterization of an alternative open reading frame protein for the calicivirus family. The immune regulatory function of the MNV VF1 protein provide important perspectives for future research into norovirus biology and pathogenesis.
Indexed as
Identifiers
What OpenQuestion holds
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.