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Dominant HPAIV H5N1 genotypes of Germany 2021/2022 are linked to high virulence in Pekin ducklings
Highly pathogenic avian influenza viruses (HPAIV) of H5 clade 2.3.4.4b pose an ongoing threat worldwide. It remains unclear whether this panzootic situation would favor low virulent phenotypes expected by the ‘avirulence hypothesis’ of viral evolution. Assessing virulence in Pekin ducklings in an intramuscular infection model revealed that the two genotypes that dominated the epidemiological situation in Germany during the period 2021 and 2022 (EU-RL:CH and EU-RL:AB) were of high virulence. In contrast, rare genotypes were of intermediate virulence. The genetic constellation of these reassortants pointed to an important role of the viral polymerase complex (RdRP), particularly the PB1 genome segment, in shaping virulence in ducklings. Occulo-nasal infection of ducklings confirmed the phenotypes for two representative viruses and indicated a more efficient replication for the high virulence strain. These observations would be in line with the ‘virulence-transmission trade-off’ model for describing HPAIV epidemiology in wild birds in Germany.
The threat of avian influenza H5N1 looms over global biodiversity
Implications for conservation Worryingly, 16% of wild bird species and 27% of mammal species with known H5N1 infections as of 2024 are already of conservation…
Coevolution between marine Aeromonas and phages reveals temporal trade-off patterns of phage resistance and host population fitness
Coevolution of bacteria and phages is an important host and parasite dynamic in marine ecosystems, contributing to the understanding of bacterial community diversity. On the time scale, questions remain concerning what is the difference between phage resistance patterns in marine bacteria and how advantageous mutations gradually accumulate during coevolution. In this study, marine Aeromonas was co-cultured with its phage for 180 days and their genetic and phenotypic dynamics were measured every 30 days. We identified 11 phage resistance genes and classified them into three categories: lipopolysaccharide (LPS), outer membrane protein (OMP), and two-component system (TCS). LPS shortening and OMP mutations are two distinct modes of complete phage resistance, while TCS mutants mediate incomplete resistance by repressing the transcription of phage genes. The co-mutation of LPS and OMP was a major mode for bacterial resistance at a low cost. The mutations led to significant reductions in the growth and virulence of bacterial populations during the first 60 days of coevolution, with subsequent leveling off. Our findings reveal the marine bacterial community dynamics and evolutionary trade-offs of phage resistance during coevolution, thus granting further understanding of the interaction of marine microbes.
Molecules-mediated bidirectional interactions between microbes and human cells
Complex molecules-mediated interactions, which are based on the bidirectional information exchange between microbes and human cells, enable the defense against diseases and health maintenance. Recently, diverse single-direction interactions based on active metabolites, immunity factors, and quorum sensing signals have largely been summarized separately. In this review, according to a simplified timeline, we proposed the framework of Molecules-mediated Bidirectional Interactions (MBI) between microbe and humans to decipher and understand their intricate interactions systematically. About the microbe-derived interactions, we summarized various molecules, such as short-chain fatty acids, bile acids, tryptophan catabolites, and quorum sensing molecules, and their corresponding human receptors. Concerning the human-derived interactions, we reviewed the effect of human molecules, including hormones, cytokines, and other circulatory metabolites on microbial characteristics and phenotypes. Finally, we discussed the challenges and trends for developing and deciphering molecule-mediated bidirectional interactions and their potential applications in the guard of human health.
Family-based genome-wide association study designs for increased power and robustness
Family-based genome-wide association studies (FGWASs) use random, within-family genetic variation to remove confounding from estimates of direct genetic effects (DGEs). Here we introduce a ‘unified estimator’ that includes individuals without genotyped relatives, unifying standard and FGWAS while increasing power for DGE estimation. We also introduce a ‘robust estimator’ that is not biased in structured and/or admixed populations. In an analysis of 19 phenotypes in the UK Biobank, the unified estimator in the White British subsample and the robust estimator (applied without ancestry restrictions) increased the effective sample size for DGEs by 46.9% to 106.5% and 10.3% to 21.0%, respectively, compared to using genetic differences between siblings. Polygenic predictors derived from the unified estimator demonstrated superior out-of-sample prediction ability compared to other family-based methods. We implemented the methods in the software package snipar in an efficient linear mixed model that accounts for sample relatedness and sibling shared environment.
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