ArticlePLoS pathogens2019
Infectious vaccine-derived rubella viruses emerge, persist, and evolve in cutaneous granulomas of children with primary immunodeficiencies.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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58 citing papers in PubMed, 89 citations in OpenAlex.
- APOBEC3A is the predominant global editor of cytosines in human mRNAs and in single-strand RNA viruses.G3 (Bethesda, Md.) · 2026Article
- Fatal Systemic Granulomatous Disease Associated with Vaccine-Derived Rubella Virus in AIOLOS-Associated Immunodeficiency.Journal of clinical immunology · 2026Article
- APOBEC3A is the predominant global editor of cytosines in human mRNAs and in single-strand RNA viruses.bioRxiv : the preprint server for biology · 2026Article
- How I Treat: Infections and inborn errors of immunity-Prevention, diagnosis, and treatment.Journal of human immunity · 2026Review
- Measles and rubella: From global health challenges to advancements in molecular diagnostics in the elimination era.Molecular therapy. Nucleic acids · 2025Review
- TAP-I Deficiency Presenting With Chronic Granulomatous Rubella Virus-Driven Cutaneous Ulceration: A Case Report and Scoping Literature Review.Journal of clinical immunology · 2025Article
- Current infectious disease management challenges in inborn errors of immunity.Annals of clinical microbiology and antimicrobials · 2025Review
- Rubella-associated granuloma in a patient with a compound heterozygous RAG1 defect and review of the literature.Immunologic research · 2025Review
- Article
- Granuloma and persistent detection of wild-type rubella virus in an immunocompromised patient.Microbiology spectrum · 2025Article
- An Expanding Universe of Mutational Signatures and Its Rapid Evolution in Single-Stranded RNA Viruses.Molecular biology and evolution · 2025Article
- Virus Evolution in Prolonged Infections of Immunocompromised Individuals.Clinical chemistry · 2025Review
- Clinical and immunological spectrum of MHC class I deficiency: insights from a long-term cohort with two novel mutations.Frontiers in immunology · 2025Article
- C→U transition biases in SARS-CoV-2: still rampant 4 years from the start of the COVID-19 pandemic.mBio · 2024Article
- Neutralization of Rubella Vaccine Virus and Immunodeficiency-Related Vaccine-Derived Rubella Viruses by Intravenous Immunoglobulins.The Journal of infectious diseases · 2024Article
- Pathogen-Agnostic Advanced Molecular Diagnostic Testing for Difficult-to-Diagnose Clinical Syndromes-Results of an Emerging Infections Network Survey of Frontline US Infectious Disease Clinicians, May 2023.Open forum infectious diseases · 2024Article
- Building Quality Control for Molecular Assays in the Global Measles and Rubella Laboratory Network.Vaccines · 2024Review
- Exploring the Role of Clustered Mutations in Carcinogenesis and Their Potential Clinical Implications in Cancer.International journal of molecular sciences · 2024Review
- Rubella virus-associated cutaneous granulomatous disease in an immunocompetent woman.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2024Article
- Rubella virus chronic inflammatory disease and other unusual viral phenotypes in inborn errors of immunity.Immunological reviews · 2024Review
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Authors and funding
19 authors at 10 institutions in 2 countries.
Funding
Abstract
Rubella viruses (RV) have been found in an association with granulomas in children with primary immune deficiencies (PID). Here, we report the recovery and characterization of infectious immunodeficiency-related vaccine-derived rubella viruses (iVDRV) from diagnostic skin biopsies of four patients. Sequence evolution within PID hosts was studied by comparison of the complete genomic sequences of the iVDRVs with the genome of the vaccine virus RA27/3. The degree of divergence of each iVDRV correlated with the duration of persistence indicating continuous intrahost evolution. The evolution rates for synonymous and nonsynonymous substitutions were estimated to be 5.7 x 10-3 subs/site/year and 8.9 x 10-4 subs/site/year, respectively. Mutational spectra and signatures indicated a major role for APOBEC cytidine deaminases and a secondary role for ADAR adenosine deaminases in generating diversity of iVDRVs. The distributions of mutations across the genes and 3D hotspots for amino acid substitutions in the E1 glycoprotein identified regions that may be under positive selective pressure. Quasispecies diversity was higher in granulomas than in recovered infectious iVDRVs. Growth properties of iVDRVs were assessed in WI-38 fibroblast cultures. None of the iVDRV isolates showed complete reversion to wild type phenotype but the replicative and persistence characteristics of iVDRVs were different from those of the RA27/3 vaccine strain, making predictions of iVDRV transmissibility and teratogenicity difficult. However, detection of iVDRV RNA in nasopharyngeal specimen and poor neutralization of some iVDRV strains by sera from vaccinated persons suggests possible public health risks associated with iVDRV carriers. Detection of IgM antibody to RV in sera of two out of three patients may be a marker of virus persistence, potentially useful for identifying patients with iVDRV before development of lesions. Studies of the evolutionary dynamics of iVDRV during persistence will contribute to development of infection control strategies and antiviral therapies.
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