Epidemiological and virological characteristics of influenza B: results of the Global Influenza B Study

Contains fulltext : 155189.pdf (publisher's version ) (Open Access)INTRODUCTION: Literature on influenza focuses on influenza A, despite influenza B having a large public health impact. The Global Influenza B Study aims to collect information on global epidemiology and burden of disease of influenza B since 2000. METHODS: Twenty-six countries in the Southern (n = 5) and Northern (n = 7) hemispheres and intertropical belt (n = 14) provided virological and epidemiological data. We calculated the proportion of influenza cases due to type B and Victoria and Yamagata lineages in each country and season; tested the correlation between proportion of influenza B and maximum weekly influenza-like illness (ILI) rate during the same season; determined the frequency of vaccine mismatches; and described the age distribution of cases by virus type. RESULTS: The database included 935 673 influenza cases (2000-2013). Overall median proportion of influenza B was 22.6%, with no statistically significant differences across seasons. During seasons where influenza B was dominant or co-circulated (>20% of total detections), Victoria and Yamagata lineages predominated during 64% and 36% of seasons, respectively, and a vaccine mismatch was observed in approximately 25% of seasons. Proportion of influenza B was inversely correlated with maximum ILI rate in the same season in the Northern and (with borderline significance) Southern hemispheres. Patients infected with influenza B were usually younger (5-17 years) than patients infected with influenza A. CONCLUSION: Influenza B is a common disease with some epidemiological differences from influenza A. This should be considered when optimizing control/prevention strategies in different regions and reducing the global burden of disease due to influenza

Structures of the interleukin 11 signalling complex reveal gp130 dynamics and the inhibitory mechanism of a cytokine variant

Abstract Interleukin (IL-)11, an IL-6 family cytokine, has pivotal roles in autoimmune diseases, fibrotic complications, and solid cancers. Despite intense therapeutic targeting efforts, structural understanding of IL-11 signalling and mechanistic insights into current inhibitors are lacking. Here we present cryo-EM and crystal structures of the human IL-11 signalling complex, including the complex containing the complete extracellular domains of the shared IL-6 family β-receptor, gp130. We show that complex formation requires conformational reorganisation of IL-11 and that the membrane-proximal domains of gp130 are dynamic. We demonstrate that the cytokine mutant, IL-11 Mutein, competitively inhibits signalling in human cell lines. Structural shifts in IL-11 Mutein underlie inhibition by altering cytokine binding interactions at all three receptor-engaging sites and abrogating the final gp130 binding step. Our results reveal the structural basis of IL-11 signalling, define the molecular mechanisms of an inhibitor, and advance understanding of gp130-containing receptor complexes, with potential applications in therapeutic development

Epidemiological and virological characteristics of influenza B: results of the Global Influenza B Study

INTRODUCTION Literature on influenza focuses on influenza A, despite influenza B having a large public health impact. The Global Influenza B Study aims to collect information on global epidemiology and burden of disease of influenza B since 2000. METHODS Twenty-six countries in the Southern (n = 5) and Northern (n = 7) hemispheres and intertropical belt (n = 14) provided virological and epidemiological data. We calculated the proportion of influenza cases due to type B and Victoria and Yamagata lineages in each country and season; tested the correlation between proportion of influenza B and maximum weekly influenzalike illness (ILI) rate during the same season; determined the frequency of vaccine mismatches; and described the age distribution of cases by virus type. RESULTS The database included 935 673 influenza cases (2000– 2013). Overall median proportion of influenza B was 22 6%, with no statistically significant differences across seasons. During seasons where influenza B was dominant or co-circulated (>20% of total detections), Victoria and Yamagata lineages predominated during 64% and 36% of seasons, respectively, and a vaccine mismatch was observed in 25% of seasons. Proportion of influenza B was inversely correlated with maximum ILI rate in the same season in the Northern and (with borderline significance) Southern hemispheres. Patients infected with influenza B were usually younger (5–17 years) than patients infected with influenza A. CONCLUSION Influenza B is a common disease with some epidemiological differences from influenza A. This should be considered when optimizing control/prevention strategies in different regions and reducing the global burden of disease due to influenza.http://www.influenzajournal.comam201

Epidemiological and virological characteristics of influenza B: results of the Global Influenza B Study

INTRODUCTION: Literature on influenza focuses on influenza A, despite influenza B having a large public health impact. The Global Influenza B Study aims to collect information on global epidemiology and burden of disease of influenza B since 2000. METHODS: Twenty-six countries in the Southern (n = 5) and Northern (n = 7) hemispheres and intertropical belt (n = 14) provided virological and epidemiological data. We calculated the proportion of influenza cases due to type B and Victoria and Yamagata lineages in each country and season; tested the correlation between proportion of influenza B and maximum weekly influenza-like illness (ILI) rate during the same season; determined the frequency of vaccine mismatches; and described the age distribution of cases by virus type. RESULTS: The database included 935 673 influenza cases (2000-2013). Overall median proportion of influenza B was 22·6%, with no statistically significant differences across seasons. During seasons where influenza B was dominant or co-circulated (>20% of total detections), Victoria and Yamagata lineages predominated during 64% and 36% of seasons, respectively, and a vaccine mismatch was observed in ≈25% of seasons. Proportion of influenza B was inversely correlated with maximum ILI rate in the same season in the Northern and (with borderline significance) Southern hemispheres. Patients infected with influenza B were usually younger (5-17 years) than patients infected with influenza A. CONCLUSION: Influenza B is a common disease with some epidemiological differences from influenza A. This should be considered when optimizing control/prevention strategies in different regions and reducing the global burden of disease due to influenza

Epidemiological and virological characteristics of influenza B: results of the Global Influenza B Study

Introduction Literature on influenza focuses on influenza A, despite influenza B having a large public health impact. The Global Influenza B Study aims to collect information on global epidemiology and burden of disease of influenza B since 2000

Reaction hijacking of tyrosine tRNA synthetase as a new whole-of-life-cycle antimalarial strategy.

Aminoacyl transfer RNA (tRNA) synthetases (aaRSs) are attractive drug targets, and we present class I and II aaRSs as previously unrecognized targets for adenosine 5-monophosphate-mimicking nucleoside sulfamates. The target enzyme catalyzes the formation of an inhibitory amino acid-sulfamate conjugate through a reaction-hijacking mechanism. We identified adenosine 5-sulfamate as a broad-specificity compound that hijacks a range of aaRSs and ML901 as a specific reagent a specific reagent that hijacks a single aaRS in the malaria parasite Plasmodium falciparum, namely tyrosine RS (PfYRS). ML901 exerts whole-life-cycle-killing activity with low nanomolar potency and single-dose efficacy in a mouse model of malaria. X-ray crystallographic studies of plasmodium and human YRSs reveal differential flexibility of a loop over the catalytic site that underpins differential susceptibility to reaction hijacking by ML901