Genetic variability of human metapneumo‐ and bocaviruses in children with respiratory tract infections

Objectives

The genotypic analysis of human metapneumo-(HMPV) and boca-(HBoV) viruses circulating in Greece and their comparison to reference and other clinical strains.

Design

Genetic analysis of representative strains over three consecutive winter seasons of the years 2005–2008.

Setting

Representative positive specimens for HMPV and HBoV from paediatric patients of healthcare units and hospitals in Southern Greece with influenza-like illness or other respiratory tract infections.

Sample

Seven to ten positive specimens for either HMPV or HBoV from each winter period. In total, 24 specimens positive for HMPV and 26 for HBoV, respectively.

Main outcome measures

Sequence diversity of HMPV and HBoV strains by sequencing the complete G and VP1/VP2 genes, respectively.

Results

In total, 24 HMPV strains were found to have a 92–100% nucleotide and a 85.9–100% amino acid identity. Phylogenetic analysis based on the number of amino acid differences, revealed circulation of 4 different subclusters belonging to genetic lineage B2. Similarly, analysis of 26 HBoV strains indicated that 22 clustered within genotype St2, 2 into genotype St1 and the remaining 2 formed a third cluster derived from potential recombination between different St1 genotype strains. St2 HBoV genotype was observed throughout the whole observation period whereas St1 only during the second and the third winter period. Higher levels of heterogeneity were observed between HMPV compared to HBoV strains.

Conclusions

Phylogenetic analysis revealed circulation of one single lineage (B2) for HMPV viruses and predominance of St2 genotype for HBoV viruses. A possible recombination between St1 genotype strains of HBoV was observed.     

Control of bone resorption in mice by Schnurri-3

Mice lacking the large zinc finger protein Schnurri-3 (Shn3) display increased bone mass, in part, attributable to augmented osteoblastic bone formation. Here, we show that in addition to regulating bone formation, Shn3 indirectly controls bone resorption by osteoclasts in vivo. Although Shn3 plays no cell-intrinsic role in osteoclasts, Shn3-deficient animals show decreased serum markers of bone turnover. Mesenchymal cells lacking Shn3 are defective in promoting osteoclastogenesis in response to selective stimuli, likely attributable to reduced expression of the key osteoclastogenic factor receptor activator of nuclear factor-κB ligand. The bone phenotype of Shn3-deficient mice becomes more pronounced with age, and mice lacking Shn3 are completely resistant to disuse osteopenia, a process that requires functional osteoclasts. Finally, selective deletion of Shn3 in the mesenchymal lineage recapitulates the high bone mass phenotype of global Shn3 KO mice, including reduced osteoclastic bone catabolism in vivo, indicating that Shn3 expression in mesenchymal cells directly controls osteoblastic bone formation and indirectly regulates osteoclastic bone resorption.     

Post‒cataract surgery endophthalmitis outbreak caused by multidrug-resistant Pseudomonas aeruginosa

In June 2010, a severe outbreak of 13 cases of post-cataract surgery endophthalmitis caused by multidrug-resistant Pseudomonas aeruginosa occurred. Pulse-field gel electrophoresis in eye isolates found 95% genetic similarity; however, extensive environmental and carriage investigation revealed no source of infection.     

Dysregulation of innate immunity in hepatitis C virus genotype 1 IL28B-unfavorable genotype patients: impaired viral kinetics and therapeutic response

Recent studies have shown that a single-nucleotide polymorphism upstream of the interleukin-28B (IL28B) gene plays a major role in predicting therapeutic response in hepatitis C virus (HCV)-infected patients treated with pegylated interferon (PEG-IFN)/ribavirin. We sought to investigate the mechanism of the IL28B polymorphism, specifically as it relates to early HCV viral kinetics, IFN pharmacokinetics, IFN pharmacodynamics, and gene expression profiles. Two prospective cohorts (human immunodeficiency virus [HIV]/HCV-coinfected and HCV-monoinfected) completing treatment with IFN/ribavirin were enrolled. Patients were genotyped at the polymorphic site rs12979860. In the HIV/HCV cohort, frequent serum sampling was completed for HCV RNA and IFN levels. DNA microarray of peripheral blood mononuclear cells and individual expression of IFN-stimulated genes (ISGs) were quantified on IFN therapy. The IL28B-favorable (CC) genotype was associated with improved therapeutic response compared with unfavorable (CT or TT) genotypes. Patients with a favorable genotype had greater first- and second-phase viral kinetics (P = 0.004 and P = 0.036, respectively), IFN maximum antiviral efficiency (P = 0.007) and infected cell death loss (P = 0.009) compared with unfavorable genotypes. Functional annotation analysis of DNA microarray data was consistent with depressed innate immune function, particularly of natural killer cells, from patients with unfavorable genotypes (P <0.004). Induction of innate immunity genes was also lower in unfavorable genotypes. ISG expression at baseline and induction with IFN was independent of IL28B genotype. CONCLUSION: Carriers of the IL28B-favorable genotype were more likely to have superior innate immune response to IFN therapy compared with unfavorable genotypes, suggesting that the unfavorable genotype has aberrant baseline induction of innate immune response pathways resulting in impaired virologic response. IL28B genotype is associated with more rapid viral kinetics and improved treatment response outcomes independent of ISG expression.     

Cross sectional area reference values for sonography of peripheral nerves and brachial plexus

ObjectiveUltrasound measurements of the cross sectional area (CSA) variability have been recently introduced to quantify pathological changes in peripheral nerves (PN).MethodsReference values from 75 healthy subjects and their correlation to age, height, weight and sex are reported.ResultsThe mean values in PN were: (1) intranerve CSA-variability: median 1.05 (SD ± 0.13), ulnar 1.53 (SD ± 0.51), fibular 1.33 (SD ± 0.37), tibial 1.39 (SD ± 0.39), (2) internerve CSA-variability 1.76 (SD ± 0.37), (3) intraplexus CSA-variability 1.52 (SD ± 0.37), (4) side-to-side difference ratio of the CSA-variability: median 1.21 (SD ± 0.04), ulnar 1.2 (SD ± 0.25), fibular 1.19 (SD ± 0.23), tibial 1.28 (SD ± 0.24) and brachial plexus 1.19 (SD ± 0.23). CSA did not correlate with height in PN, but correlated with weight in the ulnar nerve [Guyon’s canal, r = 0.411, p = 0.0237, elbow r = 0.409, p = 0.0248]. Significant changes between sex were found only in the ulnar (Guyon’s canal, p = 0.0265), fibular (popliteal fossa, p = 0.0336) and sural nerve (p = 0.048). CSA decreased with age in the median (axilla, p = 0.0236), and radial nerve (spiral groove, p = 0.0037) and increased in the tibial nerve (ankle, p < 0.0001).ConclusionsThe CSA reference values reported seem to correlate at certain sites with age, weight and sex but not with height.SignificanceThe new CSA variability measures may be helpful in investigating pathologies of the PN.