Status of Global Virologic Surveillance for Rubella Viruses

Abernathy, Emily; Hübschen, Judith M.; Muller, Claude P.; Jin, Li; Brown, David; Komase, Katsuhiro; Mori, Yoshio; Xu, Wenbo; Zhu, Zhen; Siqueira, Marilda M.; Shulga, Sergey V.; Тихонова, Н. Т.; Pattamadilok, Sirima; Incomserb, Patcha; Smit, Sheilagh B.; Akoua-Koffi, Chantal; Bwogi, Josephine; Lim, Wilina; Woo, Gibson K. S.; Triki, H.; Jee, Youngmee; Mulders, Mick N.; Filippis, Ana María Bispo de; Ahmed, Hinda; Ramamurty, Nalini; Featherstone, David; Icenogle, Joseph P.

doi:10.1093/infdis/jir099

Cited by 55 publications

(48 citation statements)

References 20 publications

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“…62, 63, 64 The sensitivity of the RT-PCR system used to generate sequencing templates from infected tissue culture cells is not critical, since the amount of rubella viral RNA in rubella virus infected cells is higher than in clinical specimens.…”

Section: New Laboratory Diagnosticsmentioning

confidence: 99%

Rubella

et al. 2015

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Rubella remains an important pathogen globally with approximately 100,000 cases of congenital rubella syndrome estimated to occur each year. Rubella vaccine is highly effective and safe when used across a population and, as a result, endemic rubella transmission has been interrupted in the Americas since 2009. Incomplete rubella vaccination programs result in continued disease transmission as evidenced by recent large outbreaks in Japan and elsewhere. Herein, we provide current results regarding rubella control, elimination and eradication policies, and a brief review of new laboratory diagnostics. In addition, we provide novel information regarding rubella vaccine immunogenetics and review the emerging evidence of inter-individual variability in humoral and cell-mediated innate and adaptive immune responses to rubella vaccine and their association with HLA alleles, haplotypes, and single nucleotide polymorphisms across the human genome. Finally, we conclude with a call for further research in rubella vaccine immunogenetics and its ability to inform a vaccinomics-level approach to novel vaccine candidate development and the need for a next generation vaccine that is affordable, easy to administer, and does not require a cold chain for optimal immunogenicity.

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Section: New Laboratory Diagnosticsmentioning

confidence: 99%

Rubella

et al. 2015

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“…Clade 2 genotypes were presumably restricted to Asia until the 2000s [10]. However, genotype 2B viruses have subsequently become widely distributed geographically, and together with 1E and 1G, are the genotypes most frequently found among the more recent samples [11]. …”

Section: Introductionmentioning

confidence: 99%

The influence of secondary structure, selection and recombination on rubella virus nucleotide substitution rate estimates

Cloete

Tanov

Muhire

et al. 2014

Virol J

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BackgroundAnnually, rubella virus (RV) still causes severe congenital defects in around 100 000 children globally. An attempt to eradicate RV is currently underway and analytical tools to monitor the global decline of the last remaining RV lineages will be useful for assessing the effectiveness of this endeavour. RV evolves rapidly enough that much of this information might be inferable from RV genomic sequence data.MethodsUsing BEASTv1.8.0, we analysed publically available RV sequence data to estimate genome-wide and gene-specific nucleotide substitution rates to test whether current estimates of RV substitution rates are representative of the entire RV genome. We specifically accounted for possible confounders of nucleotide substitution rate estimates, such as temporally biased sampling, sporadic recombination, and natural selection favouring either increased or decreased genetic diversity (estimated by the PARRIS and FUBAR methods), at nucleotide sites within the genomic secondary structures (predicted by the NASP method).ResultsWe determine that RV nucleotide substitution rates range from 1.19 × 10-3 substitutions/site/year in the E1 region to 7.52 × 10-4 substitutions/site/year in the P150 region. We find that differences between substitution rate estimates in different RV genome regions are largely attributable to temporal sampling biases such that datasets containing higher proportions of recently sampled sequences, will tend to have inflated estimates of mean substitution rates. Although there exists little evidence of positive selection or natural genetic recombination in RV, we show that RV genomes possess pervasive biologically functional nucleic acid secondary structure and that purifying selection acting to maintain this structure contributes substantially to variations in estimated nucleotide substitution rates across RV genomes.ConclusionBoth temporal sampling biases and purifying selection favouring the conservation of RV nucleic acid secondary structures have an appreciable impact on substitution rate estimates but do not preclude the use of RV sequence data to date ancestral sequences. The combination of uniformly high substitution rates across the RV genome and strong temporal structure within the available sequence data, suggests that such data should be suitable for tracking the demographic, epidemiological and movement dynamics of this virus during eradication attempts.Electronic supplementary materialThe online version of this article (doi:10.1186/1743-422X-11-166) contains supplementary material, which is available to authorized users.

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“…There are only a few studies which used extracted RNAs for some [19] or even all RV genotypes [2] to validate RT-qPCR assays. Although our study lacks some of the RV genotypes, the three currently circulating genotypes (1E, 1G, and 2B) with a global distribution are included [1,23]. Furthermore, an in-depth and comprehensive in silico The assay involved ten-fold serial dilutions of the RNA extracted from cell culture supernatants infected with the indicated RV genotypes.…”

Section: Discussionmentioning

confidence: 99%

“…Clade 2 comprises three recognized genotypes (2A, 2B, and 2C). While most RV genotypes have a more restricted geographic distribution, genotypes 1E and 1G, as well as 2B, are found worldwide [1,28]. Despite the existence of an effective vaccine and a high overall RV immunization coverage in many European countries, susceptible cohorts with low vaccine-acquired immunity might represent a continuous risk for importation of RV from its endemic areas [18,24].…”

Section: Introductionmentioning

confidence: 99%

A sensitive one-step TaqMan amplification approach for detection of rubella virus clade I and II genotypes in clinical samples

et al. 2016

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Although teratogenic rubella virus (RV) causes a vaccine-preventable disease, it is still endemic in several countries worldwide. Thus, there is a constant risk of RV importation into non-endemic areas. RV monitoring, especially during measles and Zika virus outbreaks, requires reliable diagnostic tools. For this study, a TaqMan-based one-step reverse transcription-quantitative PCR (RT-qPCR) assay, with the p90 gene as a novel and so far unexplored target for detection of clade I and II genotypes, was developed and evaluated. Automated nucleic acid extraction was carried out. Performance characteristics of the TaqMan RT-qPCR assay were determined for a RV plasmid standard and RNA extracted from virus-infected cell culture supernatants representing clade I and II genotypes. Diagnostic specificity and sensitivity were validated against other RNA and DNA viruses, relevant for RV diagnostic approaches and for RV-positive clinical samples, respectively. The assay is specific and highly sensitive with a limit of detection as low as five to one copies per reaction or 200 infectious virus particles per ml. The coefficients of variation (CV) were specified as intra-(within one run) and inter-(between different runs) assay variation, and calculated based on the standard deviations for the obtained Ct values of the respective samples. Intraand inter-assay CV values were low, with a maximum of 3.4% and 2.4%, respectively. The assay was shown to be suitable and specific for the analysis of clinical samples. With p90 as a novel target, the highly sensitive and specific TaqMan assay outlined in this study is suitable for RV diagnosis worldwide.

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Status of Global Virologic Surveillance for Rubella Viruses

Cited by 55 publications

References 20 publications

Rubella

Rubella

The influence of secondary structure, selection and recombination on rubella virus nucleotide substitution rate estimates

A sensitive one-step TaqMan amplification approach for detection of rubella virus clade I and II genotypes in clinical samples

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