The incidence and prevalence of IgA nephropathy in Europe.

BACKGROUND: This study aimed to determine the incidence and prevalence of immunoglobulin A nephropathy (IgAN) in Europe based on high-quality data from national registries. METHODS: IgAN incidences were obtained from a literature review of European studies of national kidney biopsy registry data in which IgAN diagnosis was biopsy-verified using contemporary techniques. Studies were eligible for the main analysis if published from 1990 to 2020. IgAN point prevalence was defined as the annual IgAN incidence multiplied by the estimated duration of disease. Incidence and prevalence estimates were made for three pooled populations: (i) patients of all ages; (ii) pediatric patients; and (iii) elderly patients. RESULTS: Across 10 European countries, the estimated annual IgAN incidence was 0.76 per 100 000 in patients of all ages. The corresponding pooled IgAN point prevalence was 2.53 per 10 000 (95% confidence interval: 2.51-2.55), ranging from 1.14 per 10 000 in Spain to 5.98 per 10 000 in Lithuania. Applied to 2021 population estimates, the number of expected prevalent IgAN cases was 47 027 across all 10 countries and ranged from 577 in Estonia to 16 645 in Italy. Among pediatric patients, IgAN incidence was 0.20 per 100 000 children and IgAN point prevalence was 0.12 per 10 000 children. Among elderly patients, IgAN incidence was 0.30 per 100 000 and IgAN point prevalence was 0.36 per 10 000. CONCLUSIONS: Based on high-quality data from European national registries, IgAN point prevalence was estimated at 2.53 per 10 000 in patients of all ages. Prevalence was considerably lower in pediatric and elderly populations.

Dual Insect specific virus infection limits Arbovirus replication in Aedes mosquito cells.

Aedes mosquitoes are vectors for many pathogenic viruses. Cell culture systems facilitate the investigation of virus growth in the mosquito vector. We found Zika virus (ZIKV) growth to be consistent in A. albopictus cells but hypervariable in A. aegypti cell lines. As a potential explanation of this variability, we tested the hypothesis that our cells harbored opportunistic viruses. We screened Aedes cell lines for the presence of insect specific viruses (ISVs), Cell-fusing agent virus (CFAV) and Phasi charoen-like virus (PCLV). PCLV was present in the ZIKV-growth-variable A. aegypti cell lines but absent in A. albopictus lines, suggesting that these ISVs may interfere with ZIKV growth. In support of this hypothesis, PCLV infection of CFAV-positive A. albopictus cells inhibited the growth of ZIKV, dengue virus and La Crosse virus. These data suggest ISV infection of cell lines can impact arbovirus growth leading to significant changes in cell permissivity to arbovirus infection.

Group B Wolbachia Strain-Dependent Inhibition of Arboviruses.

Mosquito-borne viruses, including Zika virus (ZIKV) and dengue virus (DENV), are global threats that continue to infect millions annually. Historically, efforts to combat the spread of these diseases have sought to eradicate the mosquito population. This has had limited success. Recent efforts to combat the spread of these diseases have targeted the mosquito population and the mosquito's ability to transmit viruses by altering the mosquito's microbiome. The introduction of particular strains of Wolbachia bacteria into mosquitos suppresses viral growth and blocks disease transmission. This novel strategy is being tested worldwide to reduce DENV and has early indications of success. The Wolbachia genus comprised divergent strains that are divided in major phylogenetic clades termed supergroups. All Wolbachia field trials currently utilize supergroup A Wolbachia in Aedes aegypti mosquitos to limit virus transmission. Here we discuss our studies of Wolbachia strains not yet used in virus control strategies but that show strong potential to reduce ZIKV replication. These strains are important opportunities in the search for novel tools to reduce the levels of mosquito-borne viruses and provide additional models for mechanistic studies.

The Gut Commensal Microbiome of Drosophila melanogaster Is Modified by the Endosymbiont Wolbachia.

Endosymbiotic Wolbachia bacteria and the gut microbiome have independently been shown to affect several aspects of insect biology, including reproduction, development, life span, stem cell activity, and resistance to human pathogens, in insect vectors. This work shows that Wolbachia bacteria, which reside mainly in the fly germline, affect the microbial species present in the fly gut in a lab-reared strain. Drosophila melanogaster hosts two main genera of commensal bacteria-Acetobacter and Lactobacillus. Wolbachia-infected flies have significantly reduced titers of Acetobacter. Sampling of the microbiome of axenic flies fed with equal proportions of both bacteria shows that the presence of Wolbachia bacteria is a significant determinant of the composition of the microbiome throughout fly development. However, this effect is host genotype dependent. To investigate the mechanism of microbiome modulation, the effect of Wolbachia bacteria on Imd and reactive oxygen species pathways, the main regulators of immune response in the fly gut, was measured. The presence of Wolbachia bacteria does not induce significant changes in the expression of the genes for the effector molecules in either pathway. Furthermore, microbiome modulation is not due to direct interaction between Wolbachia bacteria and gut microbes. Confocal analysis shows that Wolbachia bacteria are absent from the gut lumen. These results indicate that the mechanistic basis of the modulation of composition of the microbiome by Wolbachia bacteria is more complex than a direct bacterial interaction or the effect of Wolbachia bacteria on fly immunity. The findings reported here highlight the importance of considering the composition of the gut microbiome and host genetic background during Wolbachia-induced phenotypic studies and when formulating microbe-based disease vector control strategies. IMPORTANCEWolbachia bacteria are intracellular bacteria present in the microbiome of a large fraction of insects and parasitic nematodes. They can block mosquitos' ability to transmit several infectious disease-causing pathogens, including Zika, dengue, chikungunya, and West Nile viruses and malaria parasites. Certain extracellular bacteria present in the gut lumen of these insects can also block pathogen transmission. However, our understanding of interactions between Wolbachia and gut bacteria and how they influence each other is limited. Here we show that the presence of Wolbachia strain wMel changes the composition of gut commensal bacteria in the fruit fly. Our findings implicate interactions between bacterial species as a key factor in determining the overall composition of the microbiome and thus reveal new paradigms to consider in the development of disease control strategies.

Variable Inhibition of Zika Virus Replication by Different Wolbachia Strains in Mosquito Cell Cultures.

Mosquito-borne arboviruses are a major source of human disease. One strategy to reduce arbovirus disease is to reduce the mosquito's ability to transmit virus. Mosquito infection with the bacterial endosymbiont Wolbachia pipientis wMel is a novel strategy to reduce Aedes mosquito competency for flavivirus infection. However, experiments investigating cyclic environmental temperatures have shown a reduction in maternal transmission of wMel, potentially weakening the integration of this strain into a mosquito population relative to that of other Wolbachia strains. Consequently, it is important to investigate additional Wolbachia strains. All Zika virus (ZIKV) suppression studies are limited to the wMel Wolbachia strain. Here we show ZIKV inhibition by two different Wolbachia strains: wAlbB (isolated from Aedes albopictus mosquitoes) and wStri (isolated from the planthopper Laodelphax striatellus) in mosquito cells. Wolbachia strain wStri inhibited ZIKV most effectively. Single-cycle infection experiments showed that ZIKV RNA replication and nonstructural protein 5 translation were reduced below the limits of detection in wStri-containing cells, demonstrating early inhibition of virus replication. ZIKV replication was rescued when Wolbachia was inhibited with a bacteriostatic antibiotic. We observed a partial rescue of ZIKV growth when Wolbachia-infected cells were supplemented with cholesterol-lipid concentrate, suggesting competition for nutrients as one of the possible mechanisms of Wolbachia inhibition of ZIKV. Our data show that wAlbB and wStri infection causes inhibition of ZIKV, making them attractive candidates for further in vitro mechanistic and in vivo studies and future vector-centered approaches to limit ZIKV infection and spread.IMPORTANCE Zika virus (ZIKV) has swiftly spread throughout most of the Western Hemisphere. This is due in large part to its replication in and spread by a mosquito vector host. There is an urgent need for approaches that limit ZIKV replication in mosquitoes. One exciting approach for this is to use a bacterial endosymbiont called Wolbachia that can populate mosquito cells and inhibit ZIKV replication. Here we show that two different strains of Wolbachia, wAlbB and wStri, are effective at repressing ZIKV in mosquito cell lines. Repression of virus growth is through the inhibition of an early stage of infection and requires actively replicating Wolbachia Our findings further the understanding of Wolbachia viral inhibition and provide novel tools that can be used in an effort to limit ZIKV replication in the mosquito vector, thereby interrupting the transmission and spread of the virus.