RESUMEN
The lower respiratory system serves as the target and barrier for beta-coronavirus (beta-CoV) infections. In this study, we explored beta-CoV infection dynamics in human bronchial epithelial (HBE) organoids, focusing on HCoV-OC43, SARS-CoV, MERS-CoV, and SARS-CoV-2. Utilizing advanced organoid culture techniques, we observed robust replication for all beta-CoVs, particularly noting that SARS-CoV-2 reached peak viral RNA levels at 72 h postinfection. Through comprehensive transcriptomic analysis, we identified significant shifts in cell population dynamics, marked by an increase in goblet cells and a concurrent decrease in ciliated cells. Furthermore, our cell tropism analysis unveiled distinct preferences in viral targeting: HCoV-OC43 predominantly infected club cells, while SARS-CoV had a dual tropism for goblet and ciliated cells. In contrast, SARS-CoV-2 primarily infected ciliated cells, and MERS-CoV showed a marked affinity for goblet cells. Host factor analysis revealed the upregulation of genes encoding viral receptors and proteases. Notably, HCoV-OC43 induced the unfolded protein response pathway, which may facilitate viral replication. Our study also reveals a complex interplay between inflammatory pathways and the suppression of interferon responses during beta-CoV infections. These findings provide insights into host-virus interactions and antiviral defense mechanisms, contributing to our understanding of beta-CoV infections in the respiratory tract.
Asunto(s)
Coronavirus Humano OC43 , Coronavirus del Síndrome Respiratorio de Oriente Medio , Humanos , Línea Celular , Bronquios , SARS-CoV-2 , Interferones , OrganoidesRESUMEN
Severe fever with thrombocytopenia syndrome virus (SFTSV) poses a significant public health challenge in East Asia, necessitating a deeper understanding of its evolutionary dynamics to effectively manage its spread and pathogenicity. This study provides a comprehensive analysis of the genetic diversity, recombination patterns, and selection pressures across the SFTSV genome, utilizing an extensive dataset of 2041 sequences from various hosts and regions up to November 2023. Employing maximum likelihood and Bayesian evolutionary analysis by sampling trees (BEAST), we elucidated the phylogenetic relationships among nine distinct SFTSV genotypes (A, B1, B2, B3, B4, C, D, E, and F), revealing intricate patterns of viral evolution and genotype distribution across China, South Korea, and Japan. Furthermore, our analysis identified 34 potential reassortments, underscoring a dynamic genetic interplay among SFTSV strains. Genetic recombination was observed most frequently in the large segment and least in the small segment, with notable recombination hotspots characterized by stem-loop hairpin structures, indicative of a structural propensity for genetic recombination. Additionally, selection pressure analysis on critical viral genes indicated a predominant trend of negative selection, with specific sites within the RNA-dependent RNA polymerase and glycoprotein genes showing positive selection. These sites suggest evolutionary adaptations to host immune responses and environmental pressures. This study sheds light on the intricate evolutionary mechanisms shaping SFTSV, offering insights into its adaptive strategies and potential implications for vaccine development and therapeutic interventions.
RESUMEN
Heart rate variability (HRV) has been suggested to reflect executive function and related neural activity. Executive dysfunction has been suggested to play an important role in the pathophysiology of emotional disorders. The purpose of this study was to investigate whether HRV showed a significant correlation with electroencephalogram (EEG) during a working memory performance in patients with depressive or anxiety disorder. A retrospective analysis was conducted with data from 61 patients with depressive disorder (43 women and 18 men) and 59 patients with anxiety disorder (35 women and 24 men). HRV was measured in the resting state, and EEG was recorded in the resting state and during the execution of a working memory task. It was performed in patients with depressive and anxiety disorder, and the paired sample t-test between resting state and task performance, as well as the partial correlation analysis between HRV and EEG, was conducted. Both depressed and anxious patients showed weaker beta relative power during the working memory task compared to the rest period. The resting-state EEG did not correlate with HRV parameters in both groups. In depressed patients, HRV showed a positive correlation with delta power during the task and a negative correlation with beta relative power during the task. In patients with anxiety disorder, HRV showed a significant positive correlation with theta power of the right frontal region during the task. Our results suggest that HRV would be related to executive-function-related neural activity in patients with depressive or anxiety disorder. Future studies with more subjects, including healthy controls, are needed to verify the correlation between HRV and EEG and to come up with a more comprehensive picture of neurobiological changes in emotional disorders.