Association of Ocular Inflammation and Rubella Virus Persistence

Gonzales, John A.; Hinterwirth, Armin; Shantha, Jessica G.; Wang, Kaidi; Zhong, Lina; Cummings, Susie; Ying, Qian; Wilson, Michael R.; Acharya, Nisha R.; Doan, Thuy

doi:10.1001/jamaophthalmol.2018.6185

Cited by 39 publications

(30 citation statements)

References 15 publications

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“…Attempts in our and other labs to use next generation sequencing techniques for deep sequencing of RV genomes directly from clinical samples have been unsuccessful so far; sequencing depth rarely exceeded 10, probably because of low quantities of viral RNA in clinical samples, the high GC content of the RV genome, and the strong genomic secondary structure [16, 22]. Hence we characterized viral diversity by molecular cloning followed by Sanger sequencing.…”

Section: Resultsmentioning

confidence: 99%

Infectious vaccine-derived rubella viruses emerge, persist, and evolve in cutaneous granulomas of children with primary immunodeficiencies

et al. 2019

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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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Section: Resultsmentioning

confidence: 99%

Infectious vaccine-derived rubella viruses emerge, persist, and evolve in cutaneous granulomas of children with primary immunodeficiencies

et al. 2019

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“…In addition, there were specificity concerns in the original bioinformatics analysis. Of the viruses detected by Galileo that were not detected by qPCR, only 29.2% (7/24) were detected by an alternative sequence analysis pipeline (25). The viruses detected only by Galileo included CMV ( n = 6), EBV ( n = 2), HHV-6 ( n = 2), and JCV ( n = 7).…”

Section: Discussionmentioning

confidence: 99%

“…FASTQ files from clinical samples in which the Galileo and qPCR results were discrepant were analyzed using an alternative metagenomic NGS analysis pipeline (25).…”

Section: Methodsmentioning

confidence: 99%

Metagenomic Next-Generation Sequencing for Identification and Quantitation of Transplant-Related DNA Viruses

Carpenter

Watson²,

Bacher

et al. 2019

J Clin Microbiol

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“…MDS was performed as previously described. 5 Briefly, total RNA was extracted from the swabs and reverse transcribed to double-stranded complementary DNA. The complementary DNA was converted to Illumina libraries (San Diego, CA) and amplified with 16 PCR cycles.…”

Section: Metagenomic Deep Sequencing For the Diagnosis Of Corneal Andmentioning

confidence: 99%

Metagenomic Deep Sequencing for the Diagnosis of Corneal and External Disease Infections

et al. 2019

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Association of Ocular Inflammation and Rubella Virus Persistence

Abstract: This case series assesses the utility of metagenomic deep sequencing in identifying rubella virus infection in patients with uveitis.

Cited by 39 publications

References 15 publications

Infectious vaccine-derived rubella viruses emerge, persist, and evolve in cutaneous granulomas of children with primary immunodeficiencies

Infectious vaccine-derived rubella viruses emerge, persist, and evolve in cutaneous granulomas of children with primary immunodeficiencies

Metagenomic Next-Generation Sequencing for Identification and Quantitation of Transplant-Related DNA Viruses

Metagenomic Deep Sequencing for the Diagnosis of Corneal and External Disease Infections

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